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Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors

Sponsor
Seagen Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02001623
Collaborator
Genmab (Industry)
195
Enrollment
29
Locations
1
Arm
65
Actual Duration (Months)
6.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the trial is to establish the tolerability of HuMax-TF-ADC in a mixed population of patients with specified solid tumors.

Condition or Disease Intervention/Treatment Phase
  • Drug: Tisotumab Vedotin (HuMax-TF-ADC)
 Phase 1/Phase 2

Detailed Description

The study is conducted in two parts. The dose escalation portion of the trial subjects are enrolled into cohorts at increasing dose levels of HuMax-TF-ADC in 21 day treatment cycles.

In the Cohort Expansion part of the trial, will further explore the recommended phase 2 dose of HuMax-TF-ADC as determined in Part 1

Study Design

Study Type:
Interventional
Actual Enrollment :
195 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
Escalation phase for dose finding followed by expansion phaseEscalation phase for dose finding followed by expansion phase
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
First-in-human, Dose-escalating Safety Study of Tissue Factor Specific Antibody Drug Conjugate Tisotumab Vedotin (HuMax® TF ADC) in Patients With Locally Advanced and/or Metastatic Solid Tumors Known to Express Tissue Factor
Actual Study Start Date :
Nov 30, 2013
Actual Primary Completion Date :
May 2, 2019
Actual Study Completion Date :
May 2, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tisotumab Vedotin (HuMax-TF-ADC)

All arms of the trial (borh in escalation and expansion phase) will be administered tisotumab vedotin (HuMax-TF-ADC)

Drug: Tisotumab Vedotin (HuMax-TF-ADC)
Other Names:
  • TIVDAK

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events [Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the dose escalation part.]

      Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade >=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    2. Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events [Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 325 days in the dose expansion part.]

      Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade >=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    Secondary Outcome Measures

    1. Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Number of participants with markedly abnormal hematology values was defined as all participants who experienced at least 1 CTCAE grade >= 3 hematology value. A markedly abnormal hematology value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    2. Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Number of participants with markedly abnormal coagulation values was defined as all participants who experienced at least 1 CTCAE grade >= 3 coagulation value. A markedly abnormal coagulation value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    3. Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Number of participants with markedly abnormal biochemistry results were defined as all participants who experienced at least 1 CTCAE grade >= 3 biochemistry value. A markedly abnormal biochemistry value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    4. Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash [Day 1 to end of follow-up, up to a maximum of 60 weeks]

    5. Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Bleeding adverse events of special interest included treatment emergent adverse events with preferred terms within the following standardised MedDRA queries (SMQs): Haemorrhage terms, excluding laboratory terms SMQ [20000039] (Broad) and Haemorrhage, laboratory terms SMQ [20000040] (Narrow). Bleeding adverse events of special interest were evaluated according to the NCI-CTCAE version 4.03. Bleeding events of all grades are included. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    6. Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Peripheral neuropathy events of special interest were evaluated according to the NCI-CTCAE version 4.03. Peripheral neuropathy events of all grades are included in the numbers below. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

    7. Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      Pharmacokinetic (PK) parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not collected to report or calculate clearance for the expansion phase.

    8. Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the volume of distribution of tisotumab vedotin and total HuMax-TF for the dose expansion part.

    9. Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    10. Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was only analyzed in the dose escalation part of the study. Data was not planned to be collected for the AUC0-inf of tisotumab vedotin and total HuMax-TF for the dose expansion part.

    11. Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    12. Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    13. Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. t1/2 was only analyzed for the dose escalation part of the study. Data was not planned to be collected for t1/2 of tisotumab vedotin and total HuMax-TF for the dose expansion part.

    14. Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE) [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    15. Dose Escalation Part: AUC0-inf of Free MMAE [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was not planned to be collected for the dose expansion part. AUC0-inf was not calculated where the percentage of the AUC that was due to the extrapolation was more than 20%.

    16. Dose Escalation and Expansion Part: Cmax of Free MMAE [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    17. Dose Escalation and Expansion Part: Tmax of Free MMAE [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.

    18. Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE [Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)]

      PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study.

    19. Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Participants who met the criterion for positive ADAs on treatment were defined as participants who were negative at baseline and had at least one positive post-baseline result, or participants who were positive at baseline and had at least one post baseline result with a titer higher than baseline.

    20. Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Anti-tumor activity measured by the number of participants who experienced tumor shrinkage was not planned to be collected for the dose expansion part.

    21. Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Anti-tumor activity measured by maximum reduction among available post-baseline sum of lesion measurements was not planned to be collected for the dose escalation part.

    22. Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA) [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      PSA was only assessed in participants with castrate-resistant prostate cancer.

    23. Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125 [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      In the dose escalation part, CA-125 was only assessed for participants with ovarian cancer. In the dose expansion part, CA-125 was intended to be assessed only for participants with ovarian and endometrium cancer, but was additionally assessed for some participants with NSCLC and cervical cancer.

    24. Dose Escalation and Expansion Part: Objective Response Rate [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      Objective Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Response assessment was investigator based for the escalation part and Independent Review Committee (IRC) based for the expansion part.

    25. Dose Escalation and Expansion Part: Disease Control Rate [At 6, 12, 24 and 36 weeks]

      Disease control rate was defined as the percentage of participants with CR, PR or stable disease (SD) as per investigator assessment per RECIST version 1.1 after 6, 12, 24 and 36 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.

    26. Dose Escalation and Expansion Part: Progression Free Survival (PFS) [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      PFS was defined as the time in weeks from Day 1 in Cycle 1 to first disease progression or death, whichever occurred earliest, as assessed by the investigator. Only deaths that occurred within 60 days of the last visit were considered in the analysis and result are presented based on Kaplan-Meier estimates. Progression as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase from nadir in the sum of diameters of target lesions, unequivocal progression in non-target lesions, or the appearance of new lesions

    27. Dose Expansion Part: Duration of Response (DOR) [Day 1 to end of follow-up, up to a maximum of 60 weeks]

      DOR was defined as the median time in weeks from when confirmed response was first documented until the first documented disease progression, or death from any cause, whichever was earliest as assessed by the investigator. A responder was defined as any participant with a best overall response of confirmed CR or PR.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with relapsed, advanced and/or metastatic cancer who have failed available standard treatments or who are not candidates for standard therapy.

    Patients must have measurable disease

    • Age ≥ 18 years.

    • Acceptable renal function

    • Acceptable liver function

    • Acceptable hematological status (without hematologic support

    • Acceptable coagulation status

    • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • Life expectancy of at least three months.

    • A negative serum pregnancy test (if female and aged between 18-55 years old).

    • Women who are pregnant or breast feeding are not to be included.

    • Patients, both females and males, of reproductive potential must agree to use adequate contraception during and for six months after the last infusion of HuMax-TF-ADC.

    • Following receipt of verbal and written information about the study, patients must provide signed informed consent before any study-related activity is carried out.

    Exclusion Criteria:

    • Known past or current coagulation defects.

    • Ongoing major bleeding,

    • Have clinically significant cardiac disease

    • A baseline QT interval as corrected by Fridericia's formula (QTcF) > 450 msec, a complete left bundle branch block (defined as a QRS interval ≥ 120 msec in left bundle branch block form) or an incomplete left bundle branch block.

    • Have received granulocyte colony stimulating factor (G-CSF) or granulocyte/macrophage colony stimulating factor support within one week or pegylated G-CSF within two weeks before the Screening Visit.

    • Have received a cumulative dose of corticosteroid ≥ 100 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.

    • Major surgery within six weeks or open biopsy within 14 days before drug infusion.

    • Plan for any major surgery during treatment period.

    • Any history of intracerebral arteriovenous malformation, cerebral aneurysm, brain metastases or stroke.

    • Any anticancer therapy including; small molecules, immunotherapy, chemotherapy monoclonal antibodies or any other experimental drug within four weeks or five half lives, whichever is longest, before first infusion.

    • Prior treatment with bevacizumab within twelve weeks before the first infusion.

    • Radiotherapy within 28 days prior to first dose.

    • Patients who have not recovered from symptomatic side effects of radiotherapy at the time of initiation of screening procedure.

    • Known past or current malignancy other than inclusion diagnosis, except for:

    • Cervical carcinoma of Stage 1B or less.

    • Non-invasive basal cell or squamous cell skin carcinoma.

    • Non-invasive, superficial bladder cancer.

    • Prostate cancer with a current PSA level < 0.1 ng/mL.

    • Any curable cancer with a complete response (CR) of > 5 years duration.

    • Known human immunodeficiency virus seropositivity.

    • Positive serology (unless due to vaccination or passive immunization due to Ig therapy) for hepatitis B

    • Positive serology for hepatitis C based on test at screening.

    • Inflammatory bowel disease including Crohn's disease and colitis ulcerosa.

    • Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.

    • Ongoing acute or chronic inflammatory skin disease.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California Irvine Medical Center (UCIMC) Orange California United States 92868-3201
    2 Yale Cancer Center New Haven Connecticut United States 06520
    3 University of Miami Miami Florida United States 33136
    4 University Gynecologic Oncology Atlanta Georgia United States 30342
    5 Comprehensive Cancer Centers of Nevada Las Vegas Nevada United States 89169
    6 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    7 MD Anderson Cancer Center Houston Texas United States 77030
    8 University of Virginia Charlottesville Virginia United States 22908
    9 Universitair Ziekenhuis Antwerpen Edegem Antwerpen Belgium 2650
    10 Universitair Ziekenhuis Leuven Leuven Flemish Brabant Belgium 3000
    11 Grand Hôpital de Charleroi Charleroi Hainaut Belgium 6000
    12 Centre Hospitalier Universitaire Ambroise Paré Mons Hainaut Belgium 7000
    13 CHU UCL Namur - site Godinne Yvoir Namur Belgium 5530
    14 Saint-Luc University Hospital Brussels Belgium 1200
    15 CHU de Liège Liège Belgium 4000
    16 CHU UCL Namur - Sainte Elisabeth Namur Belgium 5000
    17 Rigshospitalet, Copenhagen University Hospital Copenhagen Denmark DK-2100
    18 Herlev and Gentofte Hospital Herlev Denmark 2730
    19 Karolinska Universitetssjukhuset Stockholm Solna Sweden 17176
    20 Lungemedicinska Kliniken Linköping Sweden 58185
    21 The Leeds Teaching Hospitals NHS Trust Leeds England United Kingdom LS9 7TF
    22 University College London Hospitals London England United Kingdom NW1 2BU
    23 Sarah Cannon Research Institute - London London England United Kingdom W1G 6AD
    24 Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne Newcastle United Kingdom NE7 7DN
    25 The Royal Marsden NHS Foundation Trust Sutton Surrey United Kingdom SM2 5PT
    26 Velindre NHS Trust Cardiff Wales United Kingdom CF14 2TL
    27 Beatson Cancer Centre Glasgow United Kingdom G12 OYN
    28 Guys hospital London United Kingdom SE1 9RT
    29 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX

    Sponsors and Collaborators

    • Seagen Inc.
    • Genmab

    Investigators

    • Principal Investigator: Johann de Bono, Professor, The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Seagen Inc.
    ClinicalTrials.gov Identifier:
    NCT02001623
    Other Study ID Numbers:
    • GEN701
    • innovaTV 201
    First Posted:
    Dec 5, 2013
    Last Update Posted:
    Dec 29, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Keywords provided by Seagen Inc.
    ovary cancer
    cervix cancer
    endometrium cancer
    bladder cancer
    prostate cancer (CRPC)
    esophagus cancer
    lung cancer(NSCLC)
    Squamous cell carcinoma of the head and neck (SCCHN)
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Carcinoma, Squamous Cell
    Urinary Bladder Neoplasms
    Squamous Cell Carcinoma of Head and Neck
    Uterine Cervical Neoplasms
    Esophageal Neoplasms
    Ovarian Neoplasms
    Endometrial Neoplasms
    Tisotumab vedotin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail In the dose escalation part of the study, 40 participants were screened and 27 were enrolled and received treatment. In the dose expansion part of the study, 294 participants were screened and 168 were enrolled and received treatment.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Period Title: Overall Study
    STARTED 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Completed 4 Cycles of Treatment 0 1 1 2 0 2 2 1 5 31 6 4 6 22 7
    Completed 12 Cycles of Treatment 0 1 0 1 0 0 0 0 0 3 0 0 1 1 0
    COMPLETED 0 0 0 1 0 0 0 0 0 2 0 0 1 1 0
    NOT COMPLETED 3 3 3 2 3 3 3 6 15 53 14 15 14 35 18

    Baseline Characteristics

    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer Total
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Total of all reporting groups
    Overall Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18 195
    Age, Customized (Count of Participants)
    In utero
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Preterm newborn infants (gestational age < 37 wks)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Newborns (0-27 days)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Infants and toddlers (28 days-23 months)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Children (2-11 years)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Adolescents (12-17 years)
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Adults (18-64 years)
    3
    100%
    1
    33.3%
    3
    100%
    3
    100%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    4
    66.7%
    12
    80%
    51
    92.7%
    8
    57.1%
    8
    53.3%
    9
    60%
    26
    72.2%
    4
    22.2%
    138
    70.8%
    From 65-84 years
    0
    0%
    2
    66.7%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    2
    33.3%
    3
    20%
    4
    7.3%
    6
    42.9%
    7
    46.7%
    6
    40%
    10
    27.8%
    14
    77.8%
    57
    29.2%
    85 years and over
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    1
    33.3%
    1
    33.3%
    2
    66.7%
    2
    66.7%
    3
    100%
    3
    100%
    5
    83.3%
    2
    13.3%
    55
    100%
    14
    100%
    3
    20%
    12
    80%
    36
    100%
    0
    0%
    140
    71.8%
    Male
    2
    66.7%
    2
    66.7%
    2
    66.7%
    1
    33.3%
    1
    33.3%
    0
    0%
    0
    0%
    1
    16.7%
    13
    86.7%
    0
    0%
    0
    0%
    12
    80%
    3
    20%
    0
    0%
    18
    100%
    55
    28.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    0
    0%
    0
    0%
    1
    2.8%
    0
    0%
    2
    1%
    Not Hispanic or Latino
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    15
    100%
    53
    96.4%
    13
    92.9%
    15
    100%
    15
    100%
    35
    97.2%
    18
    100%
    191
    97.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1%
    Race/Ethnicity, Customized (Count of Participants)
    White
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    15
    100%
    49
    89.1%
    14
    100%
    13
    86.7%
    13
    86.7%
    34
    94.4%
    17
    94.4%
    182
    93.3%
    Black or Asian American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    2
    1%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    5.5%
    0
    0%
    1
    6.7%
    1
    6.7%
    0
    0%
    0
    0%
    5
    2.6%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    1
    0.5%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    1
    2.8%
    0
    0%
    2
    1%
    Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    0
    0%
    0
    0%
    0
    0%
    1
    2.8%
    0
    0%
    3
    1.5%

    Outcome Measures

    1. Primary Outcome
    Title Dose Escalation Part: Evaluation of Treatment-Emergent Adverse Events
    Description Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade >=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the dose escalation part.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6
    TEAEs
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    Serious TEAEs
    2
    66.7%
    1
    33.3%
    0
    0%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    4
    66.7%
    Infusion-Related TEAEs
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    CTCAE Grade >=3 TEAEs
    2
    66.7%
    3
    100%
    1
    33.3%
    1
    33.3%
    2
    66.7%
    3
    100%
    2
    66.7%
    4
    66.7%
    TEAEs Related to Study Drug
    3
    100%
    3
    100%
    2
    66.7%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    2. Secondary Outcome
    Title Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Hematology Values
    Description Number of participants with markedly abnormal hematology values was defined as all participants who experienced at least 1 CTCAE grade >= 3 hematology value. A markedly abnormal hematology value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    2
    66.7%
    1
    33.3%
    1
    33.3%
    0
    0%
    2
    66.7%
    2
    66.7%
    0
    0%
    1
    16.7%
    0
    0%
    23
    41.8%
    0
    0%
    3
    20%
    1
    6.7%
    5
    13.9%
    3
    16.7%
    3. Secondary Outcome
    Title Dose Escalation and Expansion Parts: Number of Participants With Markedly Abnormal Coagulation Values
    Description Number of participants with markedly abnormal coagulation values was defined as all participants who experienced at least 1 CTCAE grade >= 3 coagulation value. A markedly abnormal coagulation value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    1
    6.7%
    7
    12.7%
    2
    14.3%
    0
    0%
    2
    13.3%
    5
    13.9%
    4
    22.2%
    4. Secondary Outcome
    Title Dose Escalation and Expansion Part: Number of Participants With Markedly Abnormal Biochemistry Values
    Description Number of participants with markedly abnormal biochemistry results were defined as all participants who experienced at least 1 CTCAE grade >= 3 biochemistry value. A markedly abnormal biochemistry value was determined using the CTCAE grading systems based on National Cancer Institute (NCI)-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    2
    66.7%
    1
    33.3%
    3
    100%
    0
    0%
    1
    33.3%
    0
    0%
    1
    33.3%
    2
    33.3%
    4
    26.7%
    8
    14.5%
    4
    28.6%
    6
    40%
    2
    13.3%
    9
    25%
    4
    22.2%
    5. Secondary Outcome
    Title Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Skin Rash
    Description
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    1
    33.3%
    0
    0%
    0
    0%
    2
    66.7%
    0
    0%
    2
    66.7%
    2
    66.7%
    4
    66.7%
    3
    20%
    6
    10.9%
    2
    14.3%
    2
    13.3%
    2
    13.3%
    8
    22.2%
    5
    27.8%
    6. Secondary Outcome
    Title Dose Escalation and Expansion Parts: Number of Participants Who Experienced a Bleeding Event of Special Interest
    Description Bleeding adverse events of special interest included treatment emergent adverse events with preferred terms within the following standardised MedDRA queries (SMQs): Haemorrhage terms, excluding laboratory terms SMQ [20000039] (Broad) and Haemorrhage, laboratory terms SMQ [20000040] (Narrow). Bleeding adverse events of special interest were evaluated according to the NCI-CTCAE version 4.03. Bleeding events of all grades are included. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    0
    0%
    1
    33.3%
    0
    0%
    3
    100%
    3
    100%
    3
    100%
    2
    66.7%
    5
    83.3%
    10
    66.7%
    31
    56.4%
    10
    71.4%
    7
    46.7%
    9
    60%
    27
    75%
    10
    55.6%
    7. Secondary Outcome
    Title Dose Escalation and Expansion Part: Number of Participants Who Experienced a Peripheral Neuropathy Event
    Description Peripheral neuropathy events of special interest were evaluated according to the NCI-CTCAE version 4.03. Peripheral neuropathy events of all grades are included in the numbers below. Grade 1:Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    5
    33.3%
    17
    30.9%
    6
    42.9%
    3
    20%
    5
    33.3%
    17
    47.2%
    7
    38.9%
    8. Secondary Outcome
    Title Dose Escalation Part: Clearance of Tisotumab Vedotin and Total HuMax-TF
    Description Pharmacokinetic (PK) parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not collected to report or calculate clearance for the expansion phase.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 0 3 3 3 3 3 3 5
    Tisotumab Vedotin: Cycle 1
    1.61
    (7.79)
    1.46
    (15.23)
    1.07
    (11.60)
    1.84
    (20.59)
    1.17
    (60.05)
    1.56
    (34.12)
    0.87
    (8.93)
    Tisotumab Vedotin: Cycle 2
    1.72
    (4.98)
    1.44
    (6.32)
    1.07
    (10.45)
    2.05
    (26.80)
    0.93
    (24.03)
    1.30
    (19.06)
    1.03
    (11.34)
    Total HuMax-TF: Cycle 1
    1.02
    (0.20)
    0.98
    (16.90)
    0.69
    (12.61)
    1.26
    (31.29)
    0.81
    (69.72)
    0.87
    (33.85)
    0.56
    (14.13)
    Total HuMax-TF: Cycle 2
    1.05
    (9.95)
    0.98
    (6.52)
    0.71
    (13.41)
    1.40
    (31.39)
    0.53
    (12.41)
    0.82
    (26.45)
    0.61
    (9.72)
    9. Secondary Outcome
    Title Dose Escalation Part: Volume of Distribution of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study. Data was not planned to be collected for the volume of distribution of tisotumab vedotin and total HuMax-TF for the dose expansion part.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 0 3 3 3 3 3 3 5
    Tisotumab Vedotin: Cycle 1
    68.40
    (11.84)
    70.80
    (14.54)
    63.46
    (16.87)
    86.10
    (12.38)
    81.13
    (35.60)
    92.04
    (21.62)
    61.46
    (18.07)
    Tisotumab Vedotin: Cycle 2
    76.69
    (9.53)
    69.74
    (7.99)
    62.61
    (6.03)
    99.20
    (20.82)
    70.21
    (42.93)
    74.82
    (4.19)
    72.74
    (5.79)
    Total HuMax-TF: Cycle 1
    51.55
    (1.61)
    60.27
    (17.79)
    57.38
    (8.65)
    77.55
    (10.74)
    67.26
    (50.61)
    68.69
    (30.52)
    50.69
    (7.20)
    Total HuMax-TF: Cycle 2
    55.75
    (10.80)
    57.13
    (8.90)
    58.48
    (12.66)
    84.98
    (22.85)
    50.62
    (36.02)
    60.40
    (17.48)
    58.10
    (12.31)
    10. Secondary Outcome
    Title Dose Escalation and Expansion Part: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study.
    Measure Participants 3 3 3 3 3 3 3 6 168
    Tisotumab Vedotin: Cycle 1
    2.5
    (3.1)
    15.4
    (8.2)
    25.1
    (16.9)
    45.2
    (9.3)
    33.1
    (19.0)
    63.0
    (49.3)
    52.3
    (33.1)
    84.9
    (33.7)
    79.31
    (49.40)
    Tisotumab Vedotin: Cycle 2
    2.0
    (15.7)
    9.9
    (49.1)
    25.6
    (7.1)
    45.2
    (10.1)
    29.8
    (25.1)
    42.7
    (72.7)
    62.7
    (21.5)
    86.3
    (14.4)
    68.54
    (55.49)
    Total HuMax-TF: Cycle 1
    2.9
    (0.5)
    15.4
    (53.1)
    35.0
    (18.9)
    60.4
    (13.4)
    44.9
    (27.8)
    86.7
    (54.3)
    85.9
    (36.7)
    123.0
    (34.7)
    112.70
    (45.23)
    Total HuMax-TF: Cycle 2
    2.4
    (12.3)
    14.4
    (55.4)
    35.7
    (7.1)
    58.8
    (15.5)
    40.9
    (26.2)
    60.2
    (76.6)
    92.5
    (33.4)
    133.6
    (13.9)
    114.54
    (45.83)
    11. Secondary Outcome
    Title Dose Escalation Part: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was only analyzed in the dose escalation part of the study. Data was not planned to be collected for the AUC0-inf of tisotumab vedotin and total HuMax-TF for the dose expansion part.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 0 3 3 3 3 3 3 6
    Tisotumab Vedotin: Cycle 1
    15.57
    (7.81)
    25.77
    (15.70)
    46.68
    (10.99)
    33.95
    (20.93)
    63.88
    (48.61)
    53.47
    (30.88)
    105.84
    (8.68)
    Tisotumab Vedotin: Cycle 2
    14.52
    (4.98)
    26.12
    (6.44)
    46.59
    (9.98)
    30.56
    (26.43)
    80.59
    (24.03)
    64.10
    (19.06)
    88.95
    (11.04)
    Total HuMax-TF: Cycle 1
    23.75
    (0.20)
    37.02
    (16.39)
    69.96
    (13.26)
    48.19
    (35.67)
    90.08
    (52.74)
    93.29
    (30.45)
    157.81
    (12.70)
    Total HuMax-TF: Cycle 2
    23.01
    (9.95)
    37.08
    (6.37)
    67.93
    (14.25)
    43.41
    (30.31)
    136.08
    (12.41)
    98.59
    (26.45)
    145.82
    (9.42)
    12. Secondary Outcome
    Title Dose Escalation and Expansion Part: Maximum Observed Plasma Concentration (Cmax) of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study
    Measure Participants 3 3 3 3 3 3 3 6 168
    Tisotumab Vedotin: Cycle 1
    4.78
    (12.35)
    12.20
    (9.47)
    19.81
    (17.32)
    34.67
    (18.48)
    23.12
    (21.10)
    35.42
    (39.20)
    32.30
    (22.08)
    55.53
    (10.31)
    29.1
    (34.1)
    Tisotumab Vedotin: Cycle 2
    3.85
    (27.65)
    12.51
    (11.51)
    20.25
    (5.14)
    32.38
    (7.11)
    21.84
    (24.97)
    35.92
    (30.39)
    44.30
    (0.32)
    48.79
    (26.37)
    26.1
    (41.2)
    Total HuMax-TF: Cycle 1
    4.90
    (13.00)
    11.84
    (8.31)
    17.98
    (11.64)
    29.30
    (10.14)
    23.55
    (25.16)
    30.57
    (37.42)
    38.78
    (21.77)
    58.02
    (12.77)
    39.8
    (31.1)
    Total HuMax-TF: Cycle 2
    3.96
    (21.83)
    11.54
    (8.83)
    16.90
    (1.57)
    31.33
    (8.13)
    22.11
    (21.03)
    37.71
    (42.96)
    43.40
    (6.67)
    53.67
    (19.75)
    38.3
    (33.3)
    13. Secondary Outcome
    Title Dose Escalation and Expansion Part: Time of Cmax (Tmax) of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study.
    Measure Participants 3 3 3 3 3 3 3 6 168
    Tisotumab Vedotin: Cycle 1
    1.47
    (72.74)
    1.18
    (13.03)
    1.34
    (11.77)
    1.15
    (11.66)
    1.12
    (9.55)
    1.18
    (14.30)
    1.18
    (7.45)
    1.11
    (12.52)
    1.21
    (364.12)
    Tisotumab Vedotin: Cycle 2
    1.54
    (63.29)
    1.34
    (6.27)
    1.32
    (5.96)
    1.13
    (11.18)
    1.21
    (16.61)
    2.44
    (35.75)
    1.14
    (9.29)
    1.29
    (7.55)
    1.44
    (303.89)
    Total HuMax-TF: Cycle 1
    2.20
    (49.15)
    1.18
    (13.03)
    1.34
    (11.77)
    1.15
    (11.66)
    1.12
    (9.55)
    1.18
    (14.30)
    1.18
    (7.45)
    1.11
    (12.52)
    1.10
    (397.92)
    Total HuMax-TF: Cycle 2
    2.19
    (46.56)
    1.34
    (6.27)
    1.32
    (5.96)
    1.13
    (11.18)
    1.21
    (16.61)
    1.76
    (50.43)
    1.14
    (9.29)
    1.29
    (7.55)
    1.15
    (356.23)
    14. Secondary Outcome
    Title Dose Escalation Part: Half-life (t1/2) of Tisotumab Vedotin and Total HuMax-TF
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. t1/2 was only analyzed for the dose escalation part of the study. Data was not planned to be collected for t1/2 of tisotumab vedotin and total HuMax-TF for the dose expansion part.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6
    Tisotumab Vedotin: Cycle 1
    12.22
    (11.61)
    29.53
    (4.08)
    33.72
    (6.26)
    41.06
    (6.85)
    32.42
    (20.05)
    47.89
    (25.82)
    40.93
    (11.48)
    41.19
    (34.02)
    Tisotumab Vedotin: Cycle 2
    13.54
    (5.50)
    23.50
    (39.89)
    33.68
    (1.74)
    40.44
    (4.69)
    33.62
    (14.50)
    32.15
    (62.74)
    39.89
    (23.15)
    48.93
    (5.61)
    Total HuMax-TF: Cycle 1
    16.05
    (27.93)
    28.66
    (30.64)
    42.52
    (7.48)
    57.37
    (8.65)
    42.72
    (34.62)
    57.72
    (17.47)
    54.95
    (5.32)
    55.10
    (27.36)
    Total HuMax-TF: Cycle 2
    18.34
    (8.73)
    30.71
    (27.65)
    40.37
    (4.27)
    56.77
    (9.60)
    42.18
    (25.39)
    46.24
    (53.11)
    51.06
    (9.18)
    66.05
    (10.07)
    15. Secondary Outcome
    Title Dose Escalation and Expansion Part: AUC0-t of Free Monomethyl Auristatin E (MMAE)
    Description PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study
    Measure Participants 3 3 3 3 3 3 3 6 168
    Cycle 1
    6.20
    (72.05)
    12.61
    (28.18)
    12.22
    (67.23)
    11.63
    (52.69)
    26.55
    (44.24)
    22.55
    (57.26)
    67.42
    (59.98)
    26.47
    (59.35)
    25.80
    (93.91)
    Cycle 2
    3.19
    (140.85)
    4.69
    (87.27)
    14.89
    (66.97)
    16.92
    (58.12)
    21.51
    (34.25)
    18.97
    (52.14)
    36.20
    (33.82)
    37.50
    (43.08)
    23.48
    (76.47)
    16. Secondary Outcome
    Title Dose Escalation Part: AUC0-inf of Free MMAE
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2. AUC0-inf was not planned to be collected for the dose expansion part. AUC0-inf was not calculated where the percentage of the AUC that was due to the extrapolation was more than 20%.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 2 1 2 1 2 1 1 1
    Cycle 1
    12.63
    (12.44)
    13.93
    (NA)
    16.32
    (57.56)
    20.39
    (NA)
    27.08
    (58.96)
    25.29
    (NA)
    78.31
    (NA)
    63.03
    (NA)
    Cycle 2
    22.32
    (43.62)
    31.40
    (NA)
    31.43
    (NA)
    33.23
    (NA)
    58.95
    (NA)
    17. Secondary Outcome
    Title Dose Escalation and Expansion Part: Cmax of Free MMAE
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study.
    Measure Participants 3 3 3 3 3 3 3 6 168
    Cycle 1
    0.760
    (62.505)
    1.673
    (30.756)
    1.524
    (54.491)
    1.410
    (19.149)
    2.807
    (39.398)
    2.587
    (29.172)
    6.351
    (61.505)
    4.877
    (31.350)
    3.16
    (88.30)
    Cycle 2
    1.091
    (74.293)
    1.342
    (24.320)
    2.059
    (51.470)
    2.243
    (50.367)
    2.718
    (39.492)
    2.035
    (39.785)
    3.369
    (36.875)
    4.704
    (18.856)
    2.73
    (78.69)
    18. Secondary Outcome
    Title Dose Escalation and Expansion Part: Tmax of Free MMAE
    Description PK parameters in plasma were determined based on non-compartmental methods and calculated separately for Cycle 1 and Cycle 2 in each part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Pharmacokinetics (PK) Analysis Set
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. PK was only planned to be analyzed per the dose level received, not per cancer type. So the PK data is pooled for all participants in the dose expansion part of the study.
    Measure Participants 3 3 3 3 3 3 3 6 168
    Cycle 1
    23.88
    (4.41)
    22.77
    (16.56)
    24.39
    (7.72)
    24.19
    (5.52)
    25.07
    (0.68)
    47.74
    (114.28)
    83.24
    (67.57)
    84.88
    (61.54)
    154.28
    (54.214)
    Cycle 2
    23.73
    (5.78)
    24.05
    (8.48)
    23.92
    (13.04)
    24.94
    (1.48)
    25.26
    (0.76)
    46.24
    (112.48)
    65.15
    (104.61)
    47.12
    (112.10)
    125.38
    (31.21)
    19. Secondary Outcome
    Title Dose Escalation Part: PK Parameters, T 1/2 of Free MMAE
    Description PK parameters in plasma were determined based on non compartmental methods and calculated separately for Cycle 1 and Cycle 2. T1/2 was determined only for the dose escalation part of the study.
    Time Frame Before infusion, Day 1 (pre-dose) and 0.25 to 336 hours post-dose of Cycle 1 and Cycle 2 (each cycle was 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK analysis set: all participants who had been exposed to tisotumab vedotin and had at least 1 PK assessment after first dose.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 2 1 2 1 2 1 1 1
    Cycle 1
    95.15
    (25.74)
    69.34
    (NA)
    63.98
    (2.24)
    62.58
    (NA)
    63.65
    (7.86)
    78.90
    (NA)
    57.74
    (NA)
    68.47
    (NA)
    Cycle 2
    69.65
    (3.86)
    60.71
    (NA)
    70.20
    (NA)
    78.94
    (NA)
    63.92
    (NA)
    20. Secondary Outcome
    Title Dose Escalation and Expansion Part: Number of Participants With Positive Anti-Drug Antibodies (ADAs) to Tisotumab Vedotin
    Description Participants who met the criterion for positive ADAs on treatment were defined as participants who were negative at baseline and had at least one positive post-baseline result, or participants who were positive at baseline and had at least one post baseline result with a titer higher than baseline.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    3
    5.5%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    1
    5.6%
    21. Secondary Outcome
    Title Dose Escalation Part: Anti-Tumor Activity Measured by Number of Participants Who Experienced Tumor Shrinkage
    Description Anti-tumor activity measured by the number of participants who experienced tumor shrinkage was not planned to be collected for the dose expansion part.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set: all participants who had been exposed to tisotumab vedotin in the dose escalation part.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    2
    66.7%
    1
    33.3%
    3
    50%
    22. Primary Outcome
    Title Dose Expansion Part: Evaluation of Treatment-Emergent Adverse Events
    Description Evaluation of treatment-emergent adverse events (TEAEs) includes number of participants with at least one: TEAE Serious TEAE Infusion-related TEAE Common Terminology Criteria for Adverse Events (CTCAE) grade >=3 Treatment-related TEAE A CTCAE TEAE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator per the below definitions. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
    Time Frame Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 325 days in the dose expansion part.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 15 55 14 15 15 36 18
    TEAEs
    15
    500%
    55
    1833.3%
    14
    466.7%
    15
    500%
    15
    500%
    36
    1200%
    18
    600%
    Serious TEAEs
    7
    233.3%
    26
    866.7%
    5
    166.7%
    8
    266.7%
    6
    200%
    13
    433.3%
    6
    200%
    Infusion-Related TEAEs
    1
    33.3%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    2
    66.7%
    0
    0%
    0
    0%
    CTCAE Grade >=3 TEAEs
    9
    300%
    30
    1000%
    8
    266.7%
    8
    266.7%
    10
    333.3%
    16
    533.3%
    11
    366.7%
    TEAEs Related to Study Drug
    15
    500%
    54
    1800%
    13
    433.3%
    14
    466.7%
    14
    466.7%
    36
    1200%
    18
    600%
    23. Secondary Outcome
    Title Dose Expansion Part: Anti-Tumor Activity Measured by Maximum Reduction Among Available Post-Baseline Sum of Lesion Measurements
    Description Anti-tumor activity measured by maximum reduction among available post-baseline sum of lesion measurements was not planned to be collected for the dose escalation part.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed includes all participants with baseline and one post-baseline evaluable tumor assessment
    Arm/Group Title Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 14 50 12 11 14 33 12
    Median (Full Range) [millimeter(s)]
    6.00
    -8.50
    1.00
    -2.00
    0.00
    -4.00
    -1.00
    24. Secondary Outcome
    Title Dose Escalation and Expansion Part: Percentage Change From Baseline in Prostate Specific Antigen (PSA)
    Description PSA was only assessed in participants with castrate-resistant prostate cancer.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Analyses includes all participants with castrate-resistant prostate cancer who have a baseline and end of study evaluable assessment.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 0 1 0 1 1 0 0 0 11
    Median (Full Range) [Percentage Change in PSA]
    64.35
    40.91
    3.92
    60.07
    25. Secondary Outcome
    Title Dose Escalation and Expansion Part: Percentage Change From Baseline in CA-125
    Description In the dose escalation part, CA-125 was only assessed for participants with ovarian cancer. In the dose expansion part, CA-125 was intended to be assessed only for participants with ovarian and endometrium cancer, but was additionally assessed for some participants with NSCLC and cervical cancer.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Analyses includes all participants in the dose escalation and expansion parts with ovarian cancer and some participants with NSCLC and cervical cancer in the dose expansion part who have a baseline and end of study evaluable assessment.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 0 0 0 1 0 1 1 2 8 10 3 25
    Median (Full Range) [Percentage Change]
    18.75
    -13.98
    113.71
    11.62
    -25.17
    37.85
    180.94
    73.19
    26. Secondary Outcome
    Title Dose Escalation and Expansion Part: Objective Response Rate
    Description Objective Response Rate per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Response assessment was investigator based for the escalation part and Independent Review Committee (IRC) based for the expansion part.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Number (95% Confidence Interval) [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    33
    1100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    27
    180%
    24
    43.6%
    7
    50%
    13
    86.7%
    13
    86.7%
    14
    38.9%
    0
    0%
    27. Secondary Outcome
    Title Dose Escalation and Expansion Part: Disease Control Rate
    Description Disease control rate was defined as the percentage of participants with CR, PR or stable disease (SD) as per investigator assessment per RECIST version 1.1 after 6, 12, 24 and 36 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease.
    Time Frame At 6, 12, 24 and 36 weeks

    Outcome Measure Data

    Analysis Population Description
    Full analysis set: all participants who had been exposed to tisotumab vedotin in either the dose escalation or expansion parts.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 3 3 3 3 3 6 15 55 14 15 15 36 18
    Week 6
    0
    0%
    33
    1100%
    33
    1100%
    67
    2233.3%
    33
    1100%
    100
    3333.3%
    67
    2233.3%
    50
    833.3%
    47
    313.3%
    60
    109.1%
    64
    457.1%
    40
    266.7%
    60
    400%
    72
    200%
    61
    338.9%
    Week 12
    0
    0%
    33
    1100%
    33
    1100%
    67
    2233.3%
    0
    0%
    67
    2233.3%
    33
    1100%
    0
    0%
    33
    220%
    47
    85.5%
    43
    307.1%
    20
    133.3%
    13
    86.7%
    42
    116.7%
    28
    155.6%
    Week 24
    0
    0%
    33
    1100%
    0
    0%
    33
    1100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20
    133.3%
    18
    32.7%
    21
    150%
    7
    46.7%
    13
    86.7%
    14
    38.9%
    6
    33.3%
    Week 36
    0
    0%
    33
    1100%
    0
    0%
    33
    1100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    46.7%
    11
    20%
    0
    0%
    0
    0%
    7
    46.7%
    3
    8.3%
    6
    33.3%
    28. Secondary Outcome
    Title Dose Escalation and Expansion Part: Progression Free Survival (PFS)
    Description PFS was defined as the time in weeks from Day 1 in Cycle 1 to first disease progression or death, whichever occurred earliest, as assessed by the investigator. Only deaths that occurred within 60 days of the last visit were considered in the analysis and result are presented based on Kaplan-Meier estimates. Progression as defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase from nadir in the sum of diameters of target lesions, unequivocal progression in non-target lesions, or the appearance of new lesions
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants with documented disease progression and/or death are included.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 3 3 2 2 3 2 3 3 10 41 4 10 9 26 12
    Median (95% Confidence Interval) [Weeks]
    5.1
    6.0
    6.1
    27.1
    6.1
    17.1
    12.3
    11.3
    11.0
    18.1
    NA
    10.1
    13.0
    13.0
    12.9
    29. Secondary Outcome
    Title Dose Expansion Part: Duration of Response (DOR)
    Description DOR was defined as the median time in weeks from when confirmed response was first documented until the first documented disease progression, or death from any cause, whichever was earliest as assessed by the investigator. A responder was defined as any participant with a best overall response of confirmed CR or PR.
    Time Frame Day 1 to end of follow-up, up to a maximum of 60 weeks

    Outcome Measure Data

    Analysis Population Description
    All participants who had a confirmed response of either CR or PR and were considered a responder for the study.
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small Cell Lung Cancer (NSCLC) Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Dose Escalation Part: 0.3 mg/kgEdit Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Dose Escalation Part: 0.6 mg/kgEdit Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Dose Escalation Part: 0.9 mg/kgEdit Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    Measure Participants 0 0 0 1 0 0 0 0 4 13 1 2 2 5 0
    Median (95% Confidence Interval) [Weeks]
    NA
    32.0
    18.4
    NA
    18.3
    NA
    21.4

    Adverse Events

    Time Frame Treatment emergent adverse events are reported from Day 1 to 30 days after dosing. The treatment duration ranged from 1 to 249 days in the escalation part and from 1 to 325 days in the expansion part.
    Adverse Event Reporting Description Deaths from all causes are reported from day of enrollment to end of follow up (up to maximum of 60 weeks).
    Arm/Group Title Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Arm/Group Description Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an intravenous (IV) infusion at a dose of 0.3 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.6 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 0.9 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.2 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.5 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 1.8 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.2 mg/kg of body weight. Participants with bladder cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with cervical cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with endometrial cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with esophageal cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with NSCLC received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with ovarian cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight. Participants with prostate cancer received tisotumab vedotin on Day 1 of each cycle (each treatment cycle was 21 days) as an IV infusion at a dose of 2.0 mg/kg of body weight.
    All Cause Mortality
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/15 (0%) 2/55 (3.6%) 0/14 (0%) 1/15 (6.7%) 1/15 (6.7%) 2/36 (5.6%) 1/18 (5.6%)
    Serious Adverse Events
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 2/3 (66.7%) 2/3 (66.7%) 2/3 (66.7%) 4/6 (66.7%) 7/15 (46.7%) 26/55 (47.3%) 5/14 (35.7%) 8/15 (53.3%) 6/15 (40%) 13/36 (36.1%) 6/18 (33.3%)
    Blood and lymphatic system disorders
    Anaemia 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Febrile neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Cardiac disorders
    Supraventricular extrasystoles 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ear and labyrinth disorders
    Hypoacusis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastrointestinal disorders
    Vomiting 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 4 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Abdominal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 1/18 (5.6%) 1
    Constipation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Diarrhoea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Dysphagia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Colitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Nausea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastrointestinal haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastrointestinal ulcer haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Oesophageal perforation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Small intestinal obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Subileus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Intestinal obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ascites 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastritis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Large intestinal obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    General disorders
    Malaise 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 3 0/18 (0%) 0
    Pyrexia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    General physical health deterioration 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Catheter site pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Mucosal inflammation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Fatigue 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Immune system disorders
    Hypersensitivity 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Infections and infestations
    Urinary tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Conjunctivitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Lower respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Sepsis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 1/18 (5.6%) 1
    Upper respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/36 (0%) 0 0/18 (0%) 0
    Bacterial sepsis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cellulitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Clostridium difficile colitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Kidney infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Micrococcus infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neutropenic sepsis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Pneumonia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Staphylococcal infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Urosepsis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cystitis escherichia 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Klebsiella infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Device related infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Injury, poisoning and procedural complications
    Stress fracture 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Investigations
    Blood creatinine increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Transaminases increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Metabolism and nutrition disorders
    Hyponatraemia 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 1/18 (5.6%) 1
    Hypokalaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Diabetes mellitus inadequate control 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hyperglycaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Hypoglycaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Diabetes mellitus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Muscular weakness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Musculoskeletal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pain in extremity 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Myalgia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Oesophageal cancer metastatic 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Tumour pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Nervous system disorders
    Peripheral sensorimotor neuropathy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cerebrovascular accident 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Guillain-barre syndrome 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Headache 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ischaemic stroke 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Lethargy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neuropathy peripheral 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Product Issues
    Stent malfunction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Psychiatric disorders
    Anxiety 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Insomnia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Renal and urinary disorders
    Haematuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 2/18 (11.1%) 3
    Urinary tract obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Acute kidney injury 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Reproductive system and breast disorders
    Vaginal haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Female genital tract fistula 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Epistaxis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hypoxia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pulmonary embolism 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pharyngeal haemorrhage 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Vascular disorders
    Vascular disorders 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Other (Not Including Serious) Adverse Events
    Dose Escalation Part: 0.3 mg/kg Dose Escalation Part: 0.6 mg/kg Dose Escalation Part: 0.9 mg/kg Dose Escalation Part: 1.2 mg/kg Dose Escalation Part: 1.5 mg/kg Dose Escalation Part: 1.8 mg/kg Dose Escalation Part: 2.0 mg/kg Dose Escalation Part: 2.2 mg/kg Dose Expansion Part: Bladder Cancer Dose Expansion Part: Cervical Cancer Dose Expansion Part: Endometrial Cancer Dose Expansion Part: Esophageal Cancer Dose Expansion Part: Non-Small-Cell Lung Cancer Dose Expansion Part: Ovarian Cancer Dose Expansion Part: Prostate Cancer
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 15/15 (100%) 55/55 (100%) 14/14 (100%) 15/15 (100%) 15/15 (100%) 36/36 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/3 (0%) 0 3/3 (100%) 3 1/3 (33.3%) 2 2/3 (66.7%) 2 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 3/6 (50%) 3 1/15 (6.7%) 1 13/55 (23.6%) 17 2/14 (14.3%) 2 3/15 (20%) 4 2/15 (13.3%) 2 0/36 (0%) 0 3/18 (16.7%) 6
    Neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 3/36 (8.3%) 3 1/18 (5.6%) 1
    Lymph node pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Lymphadenopathy 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neutrophilia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Febrile neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pericardial effusion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Sinus tachycardia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Tachycardia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 2/6 (33.3%) 2 0/15 (0%) 0 2/55 (3.6%) 2 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Bradycardia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ear and labyrinth disorders
    Ear congestion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Ear pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Hypoacusis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Vertigo 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Tinnitus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Eye disorders
    Dry eye 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 14/55 (25.5%) 14 6/14 (42.9%) 6 2/15 (13.3%) 2 6/15 (40%) 7 6/36 (16.7%) 6 2/18 (11.1%) 2
    Lacrimation increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 3/15 (20%) 3 2/15 (13.3%) 3 5/36 (13.9%) 5 0/18 (0%) 0
    Blepharitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 4 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 5/36 (13.9%) 5 1/18 (5.6%) 1
    Vision blurred 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 2/15 (13.3%) 2 6/36 (16.7%) 6 0/18 (0%) 0
    Conjunctival ulcer 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 4/55 (7.3%) 4 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Keratitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 5 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 2/36 (5.6%) 2 0/18 (0%) 0
    Meibomianitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 5/36 (13.9%) 5 0/18 (0%) 0
    Noninfective conjunctivitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Symblepharon 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Eye pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 2/15 (13.3%) 3 0/36 (0%) 0 0/18 (0%) 0
    Ocular hyperaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 2 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 0/36 (0%) 0 0/18 (0%) 0
    Cataract 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Conjunctival hyperaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Ulcerative keratitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Conjunctival disorder 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 3 0/18 (0%) 0
    Foreign body sensation in eyes 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 2 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Conjunctival haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 3/6 (50%) 4 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Eye pruritus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Punctate keratitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Chorioretinopathy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Open angle glaucoma 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Periorbital oedema 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Retinal vein occlusion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Eye inflammation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Eye irritation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 2/36 (5.6%) 2 0/18 (0%) 0
    Gastrointestinal disorders
    Nausea 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 3 1/3 (33.3%) 3 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 4/6 (66.7%) 4 7/15 (46.7%) 7 25/55 (45.5%) 30 7/14 (50%) 8 7/15 (46.7%) 8 10/15 (66.7%) 16 20/36 (55.6%) 30 12/18 (66.7%) 14
    Constipation 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/3 (66.7%) 3 1/3 (33.3%) 2 3/6 (50%) 3 6/15 (40%) 7 19/55 (34.5%) 21 3/14 (21.4%) 3 6/15 (40%) 8 5/15 (33.3%) 5 11/36 (30.6%) 13 9/18 (50%) 11
    Diarrhoea 2/3 (66.7%) 2 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 3 0/6 (0%) 0 3/15 (20%) 3 17/55 (30.9%) 26 6/14 (42.9%) 8 2/15 (13.3%) 4 4/15 (26.7%) 4 14/36 (38.9%) 19 5/18 (27.8%) 7
    Vomiting 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 2/6 (33.3%) 2 1/15 (6.7%) 1 18/55 (32.7%) 23 4/14 (28.6%) 6 4/15 (26.7%) 5 6/15 (40%) 6 11/36 (30.6%) 18 6/18 (33.3%) 9
    Abdominal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 2/15 (13.3%) 2 15/55 (27.3%) 17 1/14 (7.1%) 1 1/15 (6.7%) 1 2/15 (13.3%) 2 8/36 (22.2%) 9 6/18 (33.3%) 8
    Dyspepsia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 2/14 (14.3%) 2 2/15 (13.3%) 2 2/15 (13.3%) 2 4/36 (11.1%) 4 1/18 (5.6%) 1
    Dry mouth 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 4 5/14 (35.7%) 6 0/15 (0%) 0 2/15 (13.3%) 2 0/36 (0%) 0 1/18 (5.6%) 2
    Stomatitis 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 4 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 6/36 (16.7%) 7 2/18 (11.1%) 2
    Abdominal discomfort 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 4 1/14 (7.1%) 2 1/15 (6.7%) 1 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Rectal haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 5 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Abdominal pain lower 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Colitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 0/55 (0%) 0 0/14 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Dysphagia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 4/15 (26.7%) 4 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Abdominal distension 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Gingival bleeding 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 2/14 (14.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ascites 1/3 (33.3%) 4 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cheilitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Flatulence 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastritis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastrooesophageal reflux disease 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Haematemesis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Haematochezia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Haemorrhoids 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Melaena 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Mouth ulceration 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Oesophageal mucosal hyperplasia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Oesophagitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Oral pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Proctalgia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Tongue ulceration 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Salivary hypersecretion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Abdominal pain upper 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 2 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    General disorders
    Fatigue 3/3 (100%) 3 1/3 (33.3%) 3 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 3/3 (100%) 3 0/3 (0%) 0 4/6 (66.7%) 4 8/15 (53.3%) 10 29/55 (52.7%) 34 10/14 (71.4%) 12 10/15 (66.7%) 10 8/15 (53.3%) 11 15/36 (41.7%) 18 15/18 (83.3%) 16
    Pyrexia 2/3 (66.7%) 4 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 4/6 (66.7%) 4 2/15 (13.3%) 2 11/55 (20%) 13 1/14 (7.1%) 1 2/15 (13.3%) 3 0/15 (0%) 0 4/36 (11.1%) 5 0/18 (0%) 0
    Mucosal inflammation 1/3 (33.3%) 2 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 1/15 (6.7%) 1 5/55 (9.1%) 5 2/14 (14.3%) 2 0/15 (0%) 0 2/15 (13.3%) 2 2/36 (5.6%) 2 0/18 (0%) 0
    Oedema peripheral 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 2/15 (13.3%) 2 5/36 (13.9%) 5 1/18 (5.6%) 1
    Chills 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 2 3/55 (5.5%) 3 2/14 (14.3%) 2 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Malaise 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 5/36 (13.9%) 7 0/18 (0%) 0
    Asthenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 0/15 (0%) 0 3/36 (8.3%) 5 0/18 (0%) 0
    Chest pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 2/18 (11.1%) 2
    Influenza like illness 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 2/14 (14.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 2/36 (5.6%) 2 1/18 (5.6%) 1
    Peripheral swelling 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Chest discomfort 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Face oedema 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gait disturbance 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Infusion site reaction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Swelling 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Oedema 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hepatobiliary disorders
    Bile duct obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hepatitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Immune system disorders
    Hypersensitivity 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 0/36 (0%) 0 0/18 (0%) 0
    Contrast media allergy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Seasonal allergy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Infections and infestations
    Conjunctivitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 1/6 (16.7%) 1 7/15 (46.7%) 9 23/55 (41.8%) 37 6/14 (42.9%) 8 4/15 (26.7%) 5 6/15 (40%) 7 15/36 (41.7%) 19 9/18 (50%) 9
    Urinary tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 3 2/15 (13.3%) 3 11/55 (20%) 16 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 4/36 (11.1%) 6 1/18 (5.6%) 1
    Nasopharyngitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 3/36 (8.3%) 3 2/18 (11.1%) 2
    Oral herpes 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 4/36 (11.1%) 4 0/18 (0%) 0
    Upper respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 1 0/55 (0%) 0 3/14 (21.4%) 3 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 3 0/18 (0%) 0
    Oral candidiasis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 3/55 (5.5%) 3 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 1/18 (5.6%) 1
    Sinusitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 3/36 (8.3%) 3 0/18 (0%) 0
    Lower respiratory tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 0/36 (0%) 0 0/18 (0%) 0
    Rash pustular 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 3/15 (20%) 3 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Influenza 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Bronchitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Candida infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Catheter site infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Conjunctivitis bacterial 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Cystitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Eye infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Gingivitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Haemophilus infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Skin infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Tooth abscess 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Cellulitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pneumonia 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Gastroenteritis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Urethritis 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 5 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 2/18 (11.1%) 2
    Conjunctival scar 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Contusion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Eyelid contusion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pharynx radiation injury 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Skin laceration 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Sunburn 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Chemical burns of eye 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Investigations
    Weight decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 1/6 (16.7%) 1 4/15 (26.7%) 4 9/55 (16.4%) 10 4/14 (28.6%) 4 2/15 (13.3%) 2 2/15 (13.3%) 2 3/36 (8.3%) 3 6/18 (33.3%) 6
    Aspartate aminotransferase increased 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 1/15 (6.7%) 1 6/55 (10.9%) 9 3/14 (21.4%) 5 3/15 (20%) 3 2/15 (13.3%) 2 2/36 (5.6%) 2 2/18 (11.1%) 2
    Alanine aminotransferase increased 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 2/6 (33.3%) 2 0/15 (0%) 0 7/55 (12.7%) 8 3/14 (21.4%) 3 3/15 (20%) 3 1/15 (6.7%) 1 0/36 (0%) 0 2/18 (11.1%) 2
    Blood alkaline phosphatase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 2 3/15 (20%) 3 2/15 (13.3%) 2 0/36 (0%) 0 1/18 (5.6%) 2
    Blood creatinine increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 5 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 2
    Gamma-glutamyltransferase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 3/14 (21.4%) 3 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Vital dye staining cornea present 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    White blood cell count decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 3 0/15 (0%) 0 1/15 (6.7%) 2 0/36 (0%) 0 0/18 (0%) 0
    Blood creatine phosphokinase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Haemoglobin decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Platelet count decreased 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Lymphocyte count decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neutrophil count decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Blood magnesium decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Blood potassium increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Blood urea increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Blood urine present 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Body temperature increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Conjunctival staining 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Transaminases increased 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 1/36 (2.8%) 1 0/18 (0%) 0
    Blood fibrinogen increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Serum ferritin increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 4 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Activated partial thromboplastin time prolonged 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Blood lactate dehydrogenase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Blood urea decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    C-reactive protein increased 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Fibrin d dimer increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neutrophil count increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    White blood cell count increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 5/6 (83.3%) 5 3/15 (20%) 3 20/55 (36.4%) 22 5/14 (35.7%) 6 6/15 (40%) 7 5/15 (33.3%) 5 12/36 (33.3%) 13 10/18 (55.6%) 14
    Hypokalaemia 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/6 (33.3%) 2 2/15 (13.3%) 2 11/55 (20%) 14 1/14 (7.1%) 2 2/15 (13.3%) 2 2/15 (13.3%) 2 5/36 (13.9%) 6 2/18 (11.1%) 3
    Hypomagnesaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 6/55 (10.9%) 6 1/14 (7.1%) 1 2/15 (13.3%) 3 0/15 (0%) 0 4/36 (11.1%) 4 1/18 (5.6%) 1
    Dehydration 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Hyponatraemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hyperglycaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Hypocalcaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Hyperuricaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hypoalbuminaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hypophosphataemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Iron deficiency 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Vitamin d deficiency 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hyperkalaemia 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 2/55 (3.6%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hypercalcaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Musculoskeletal and connective tissue disorders
    Myalgia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 3/15 (20%) 3 5/55 (9.1%) 6 0/14 (0%) 0 2/15 (13.3%) 2 1/15 (6.7%) 1 9/36 (25%) 9 5/18 (27.8%) 5
    Arthralgia 0/3 (0%) 0 1/3 (33.3%) 3 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/6 (0%) 0 1/15 (6.7%) 1 6/55 (10.9%) 6 2/14 (14.3%) 2 0/15 (0%) 0 2/15 (13.3%) 2 6/36 (16.7%) 7 4/18 (22.2%) 5
    Back pain 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 1/15 (6.7%) 3 6/55 (10.9%) 7 2/14 (14.3%) 2 1/15 (6.7%) 1 2/15 (13.3%) 2 3/36 (8.3%) 3 5/18 (27.8%) 5
    Pain in extremity 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 7 0/14 (0%) 0 1/15 (6.7%) 1 3/15 (20%) 4 4/36 (11.1%) 5 0/18 (0%) 0
    Muscular weakness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 3/55 (5.5%) 3 1/14 (7.1%) 1 2/15 (13.3%) 2 1/15 (6.7%) 2 2/36 (5.6%) 2 2/18 (11.1%) 2
    Musculoskeletal pain 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 2 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 2/36 (5.6%) 2 1/18 (5.6%) 1
    Muscle spasms 0/3 (0%) 0 2/3 (66.7%) 2 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 3 2/36 (5.6%) 2 0/18 (0%) 0
    Musculoskeletal chest pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 2/36 (5.6%) 2 1/18 (5.6%) 1
    Bone pain 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 2/14 (14.3%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Flank pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 0/36 (0%) 0 0/18 (0%) 0
    Bursitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Muscle atrophy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Musculoskeletal stiffness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Arthritis climacteric 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Joint swelling 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Tendonitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Cancer pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Melanocytic naevus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Nervous system disorders
    Neuropathy peripheral 0/3 (0%) 0 1/3 (33.3%) 2 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 6/15 (40%) 7 16/55 (29.1%) 19 5/14 (35.7%) 5 2/15 (13.3%) 2 3/15 (20%) 3 10/36 (27.8%) 12 3/18 (16.7%) 3
    Peripheral sensory neuropathy 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 3 5/55 (9.1%) 5 2/14 (14.3%) 3 0/15 (0%) 0 1/15 (6.7%) 1 9/36 (25%) 9 1/18 (5.6%) 1
    Headache 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 5/55 (9.1%) 7 3/14 (21.4%) 3 1/15 (6.7%) 1 1/15 (6.7%) 2 5/36 (13.9%) 6 3/18 (16.7%) 3
    Lethargy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 2/36 (5.6%) 2 1/18 (5.6%) 2
    Dizziness 1/3 (33.3%) 1 1/3 (33.3%) 3 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 2 0/55 (0%) 0 1/14 (7.1%) 2 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 1/18 (5.6%) 1
    Dysgeusia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 2/36 (5.6%) 3 1/18 (5.6%) 1
    Peripheral motor neuropathy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 1/15 (6.7%) 1 2/36 (5.6%) 2 0/18 (0%) 0
    Polyneuropathy 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 3/18 (16.7%) 3
    Tremor 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Migraine 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 2 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Paraesthesia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Taste disorder 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Balance disorder 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 2 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Ataxia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Brain oedema 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Carpal tunnel syndrome 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Central pain syndrome 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Dysaesthesia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Mental impairment 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Myoclonus 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Nerve compression 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Sciatica 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Spinal cord compression 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Amputation stump pain 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Psychiatric disorders
    Insomnia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 2/15 (13.3%) 2 6/55 (10.9%) 6 2/14 (14.3%) 2 1/15 (6.7%) 1 4/15 (26.7%) 4 6/36 (16.7%) 7 2/18 (11.1%) 2
    Depressed mood 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 3/15 (20%) 3 0/36 (0%) 0 0/18 (0%) 0
    Depression 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 1/18 (5.6%) 1
    Anxiety 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Confusional state 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Mood altered 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Panic attack 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Restlessness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Sleep disorder 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Renal and urinary disorders
    Renal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Urine flow decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Haematuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 3/15 (20%) 3 5/55 (9.1%) 7 1/14 (7.1%) 2 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 3/18 (16.7%) 4
    Proteinuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 1/55 (1.8%) 1 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Urinary hesitation 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Renal impairment 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 1/18 (5.6%) 1
    Dysuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hydronephrosis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Reproductive system and breast disorders
    Vaginal haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 6/55 (10.9%) 7 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Balanoposthitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Metrorrhagia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Testicular pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Vulvovaginal dryness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 3/3 (100%) 4 2/3 (66.7%) 3 3/3 (100%) 4 2/3 (66.7%) 2 4/6 (66.7%) 5 13/15 (86.7%) 13 28/55 (50.9%) 40 11/14 (78.6%) 13 8/15 (53.3%) 10 11/15 (73.3%) 15 30/36 (83.3%) 34 12/18 (66.7%) 12
    Dyspnoea 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 3/15 (20%) 3 8/55 (14.5%) 8 3/14 (21.4%) 3 2/15 (13.3%) 2 3/15 (20%) 3 6/36 (16.7%) 7 2/18 (11.1%) 2
    Cough 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 5/55 (9.1%) 8 1/14 (7.1%) 1 3/15 (20%) 3 5/15 (33.3%) 5 3/36 (8.3%) 3 1/18 (5.6%) 1
    Nasal congestion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 5/55 (9.1%) 5 1/14 (7.1%) 1 0/15 (0%) 0 1/15 (6.7%) 1 4/36 (11.1%) 6 0/18 (0%) 0
    Dysphonia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 3/55 (5.5%) 3 1/14 (7.1%) 1 3/15 (20%) 3 1/15 (6.7%) 1 0/36 (0%) 0 1/18 (5.6%) 1
    Rhinorrhoea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 2/14 (14.3%) 2 0/15 (0%) 0 2/15 (13.3%) 2 6/36 (16.7%) 6 0/18 (0%) 0
    Oropharyngeal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 5 3/36 (8.3%) 3 0/18 (0%) 0
    Haemoptysis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 3/15 (20%) 3 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Nasal inflammation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Nasal obstruction 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Productive cough 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 3 0/36 (0%) 0 0/18 (0%) 0
    Catarrh 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Dry throat 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Dyspnoea exertional 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hiccups 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Laryngeal inflammation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Nasal crusting 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pulmonary embolism 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Pulmonary haemorrhage 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Rales 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Sinus pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Sneezing 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Pleural effusion 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Paranasal sinus hypersecretion 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pneumonia aspiration 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pneumonitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 2/3 (66.7%) 2 4/6 (66.7%) 4 3/15 (20%) 3 22/55 (40%) 22 8/14 (57.1%) 8 4/15 (26.7%) 4 7/15 (46.7%) 7 19/36 (52.8%) 19 6/18 (33.3%) 6
    Pruritus 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 3/15 (20%) 5 10/55 (18.2%) 11 2/14 (14.3%) 3 2/15 (13.3%) 3 1/15 (6.7%) 1 6/36 (16.7%) 7 1/18 (5.6%) 1
    Rash 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/6 (16.7%) 1 1/15 (6.7%) 2 7/55 (12.7%) 8 4/14 (28.6%) 4 1/15 (6.7%) 1 2/15 (13.3%) 2 6/36 (16.7%) 6 4/18 (22.2%) 5
    Dry skin 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 3 4/55 (7.3%) 4 4/14 (28.6%) 5 0/15 (0%) 0 2/15 (13.3%) 2 2/36 (5.6%) 2 1/18 (5.6%) 1
    Rash maculo-papular 1/3 (33.3%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/6 (33.3%) 2 0/15 (0%) 0 4/55 (7.3%) 4 0/14 (0%) 0 2/15 (13.3%) 2 1/15 (6.7%) 1 5/36 (13.9%) 6 1/18 (5.6%) 1
    Nail disorder 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 3/36 (8.3%) 3 0/18 (0%) 0
    Night sweats 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/15 (0%) 0 3/55 (5.5%) 3 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Acne 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 2/36 (5.6%) 2 0/18 (0%) 0
    Skin hyperpigmentation 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Rash macular 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 2
    Dermatitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Dermatitis acneiform 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Erythema 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hyperhidrosis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Nail ridging 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Onycholysis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Pain of skin 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Palmar-plantar erythrodysaesthesia syndrome 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Rash pruritic 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Skin ulcer 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Toxic skin eruption 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Urticaria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 1/18 (5.6%) 1
    Decubitus ulcer 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Skin lesion 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Vascular disorders
    Flushing 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 5/36 (13.9%) 6 0/18 (0%) 0
    Hypotension 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 4/55 (7.3%) 4 1/14 (7.1%) 1 1/15 (6.7%) 1 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Hypertension 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 2/15 (13.3%) 3 0/55 (0%) 0 0/14 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 0/36 (0%) 0 0/18 (0%) 0
    Hot flush 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Intermittent claudication 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 1/14 (7.1%) 1 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Lymphoedema 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/15 (6.7%) 1 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Orthostatic hypotension 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0
    Phlebitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/15 (0%) 0 0/55 (0%) 0 0/14 (0%) 0 0/15 (0%) 0 0/15 (0%) 0 0/36 (0%) 0 0/18 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    All proposed publications and presentations shall be submitted to the sponsor for its review at least 30 days before such presentation or publication is submitted to any third party.

    Results Point of Contact

    Name/Title Clinical Trial Information
    Organization Genmab A/S
    Phone 70202728
    Email clinicaltrials@genmab.com
    Responsible Party:
    Seagen Inc.
    ClinicalTrials.gov Identifier:
    NCT02001623
    Other Study ID Numbers:
    • GEN701
    • innovaTV 201
    First Posted:
    Dec 5, 2013
    Last Update Posted:
    Dec 29, 2021
    Last Verified:
    Nov 1, 2021