Tisotumab Vedotin (HuMax®-TF-ADC) Safety Study in Patients With Solid Tumors
Sponsor
Seagen Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02552121
Collaborator
Genmab (Industry)
33
16
1
24.4
2.1
0.1
Study Details
Study Description
Brief Summary
The purpose of the trial is to establish the tolerability of tisotumab vedotin (HuMax-TF-ADC) dosed three times every four weeks (3q4wk) in a mixed population of patients with specified solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The study is conducted in two parts. In the Dose Escalation portion of the trial, subjects are enrolled into cohorts at increasing dose levels of tisotumab vedotin (HuMax-TF-ADC) in 28 day treatment cycles.
The Cohort Expansion portion of the trial will further explore the recommended phase 2 dose of tisotumab vedotin (HuMax-TF-ADC) as determined in Part 1.
Study Design
Study Type:
Interventional
Actual Enrollment
:
33 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Dose-escalating and Cohort Expansion Safety Trial 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, 2015
Actual Primary Completion Date
:
Dec 13, 2017
Actual Study Completion Date
:
Dec 13, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tisotumab vedotin (HuMax-TF-ADC)
|
Drug: Tisotumab vedotin (HuMax-TF-ADC)
|
Outcome Measures
Primary Outcome Measures
- Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) [Baseline to end of trial (Part 2), up to 36 weeks]
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE) [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
- Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) [Baseline to end of trial (Part 2), up to 36 weeks]
A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening.
- Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events [Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks]
An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
- Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events [Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks]
An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator.
- Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
- Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events [Baseline to end of trial (Part 2), up to 36 weeks]
A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator.
- Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
- Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events [Baseline to end of trial (Part 2), up to 36 weeks]
A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment.
Secondary Outcome Measures
- Part 1: Number of Participants With Markedly Abnormal Laboratory Values [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade >=3 laboratory abnormality events.
- Part 2: Number of Participants With Markedly Abnormal Laboratory Values [Baseline to end of trial (Part 2), up to 36 weeks]
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade >=3 laboratory abnormality events.
- Part 1: Number of Participants Who Experienced a Skin Rash [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
- Part 2: Number of Participants Who Experienced a Skin Rash [Baseline to end of trial (Part 2), up to 36 weeks]
- Part 1: Number of Participants Who Experienced a Bleeding Event [Baseline to end of trial (Part 1), up to 72 weeks]
- Part 2: Number of Participants Who Experienced a Bleeding Event [Baseline to end of trial (Part 2), up to 36 weeks]
- Part 1: Number of Participants Who Experienced a Neuropathy Event [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
- Part 2: Number of Participants Who Experienced a Neuropathy Event [Baseline to end of trial (Part 2), up to 36 weeks]
- Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.
- Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion of Day 1, 8 and 15 of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
- Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.
- Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined.
- Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined.
- Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase.
- Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined.
- Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated) [0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1]
CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.
- Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated) [0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1]
Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken.
- Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) [Before infusion on Day 1, 8 and 15 of Cycle 1]
Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
- Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1]
- Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) [Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1]
Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk).
- Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) [Before infusion on Day 1, 8 and 15 of Cycle 1]
Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3.
- Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result [Baseline to end of follow-up; maximum follow-up was 24 weeks]
- Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result [Baseline to end of trial (Part 2), up to 36 weeks]
- Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage [Baseline to end of trial (Part 1), up to 72 weeks]
- Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements [Baseline to end of trial (Part 2), up to 36 weeks]
- Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study [Baseline to end of follow-up; maximum follow-up was 24 weeks]
- Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study [Baseline to end of follow-up; maximum follow-up was 24 weeks]
- Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study [Baseline to end of trial (Part 2), up to 36 week]
- Part 1: Best Overall Response (OR) [Baseline to end of trial (Part 1), up to 72 weeks]
Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Part 2: Best Overall Response (OR) [Baseline to end of trial (Part 2), up to 36 weeks]
Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
- Part 1: Number of Participants Who Experienced Disease Control [6, 12, 24 and 36 weeks post first infusion (Part 1)]
Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later.
- Part 2: Number of Participants Who Experienced Disease Control [6, 12, 24 and 36 weeks post first infusion (Part 2)]
Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later.
- Part 1: Progression Free Survival (PFS) [Baseline to end of follow-up; maximum time of follow-up was 24 weeks]
Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.
- Part 2: Progression Free Survival (PFS) [Baseline to end of trial (Part 2), up to 36 weeks]
Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest.
- Part 1: Duration of Response [Baseline to end of trial (Part 1), up to 72 weeks]
Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the date of first progressive disease (PD) or death.
- Part 2: Duration of Response [Baseline to end of trial (Part 2), up to 36 weeks]
Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the date of first progressive disease (PD) or death.
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 according to RECIST v1.1
-
Age ≥ 18 years.
-
Acceptable renal function.
-
Acceptable liver function.
-
Acceptable hematological status (hematologic support allowed under certain circumstances).
-
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.
-
Diffuse alveolar hemorrhage from vasculitis.
-
Known bleeding diathesis.
-
Ongoing major bleeding.
-
Trauma with increased risk of life-threatening 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.
-
Therapeutic anti-coagulative or long term anti-platelet treatment except use of low dose acetylsalicylic acid (ASA) up to 81 mg/day and non-ASA nonsteroidal anti-inflammatory drugs (NSAIDs).
-
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 ≥ 150 mg (prednisone or equivalent doses of corticosteroids) within two weeks before the first infusion.
-
No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium.
-
Major surgery within six weeks or open biopsy within 14 days before drug infusion.
-
Plan for any major surgery during treatment period.
-
Patients not willing or able to have a pre-trial tumor biopsy taken (the screening biopsy can be omitted if archived material is available).
-
Presence or anticipated requirement of epidural catheter in relation to infusions (within 48 hours before and after dose of trial drug).
-
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.
-
Prior therapy with a conjugated or unconjugated auristatin derivative.
-
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.
-
Breast cancer in BRCA1 or BRACA2 positive ovarian cancer patients.
-
Any curable cancer with a complete response (CR) of > 5 years duration.
-
Radiographic evidence of cavitating pulmonary lesions and tumor adjacent to or invading any large blood vessel unless approved by sponsor.
-
Ongoing, significant , uncontrolled medical condition.
-
Presence of peripheral neuropathy.
-
Active viral, bacterial or fungal infection requiring intravenous treatment with antimicrobial therapy starting less than four weeks prior to first dose.
-
Oral treatment with antimicrobial therapy starting less than two weeks prior to first dose.
-
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.
-
Active ocular surface disease at baseline (based on ophthalmological evaluation).
-
History of cicatricial conjunctivitis (as evaluated by an ophthalmologist).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 2 | Institut Jules Bordet | Bruxelles | Brussels | Belgium | 1000 |
| 3 | Universitaire Ziekenhuizen Leuven | Leuven | Flemish Brabant | Belgium | 3000 |
| 4 | Grand Hôpital de Charleroi | Charleroi | Hainaut | Belgium | 6000 |
| 5 | CHU de Liège | Liege | Liège | Belgium | 4000 |
| 6 | CHU UCL Namur - site Godinne | Yvoir | Namur | Belgium | 5530 |
| 7 | Cliniques Universitaires Saint-Luc | Brussels | Belgium | 1200 | |
| 8 | CHU UCL Namur - Sainte Elisabeth | Namur | Belgium | 5000 | |
| 9 | Rigshospitalet, Copenhagen University Hospital | Copenhagen | Denmark | DK-2100 | |
| 10 | Petz Aladár Megyei Oktató Kórház | Gyor | Gyor-Moson-Sopron | Hungary | 9023 |
| 11 | Debreceni Egyetem Klinikai Központ | Debrecen | Hajdu-Bihar | Hungary | 4032 |
| 12 | Semmelweis Egyetem Onkológiai Központ | Budapest | Hungary | 1083 | |
| 13 | University College London Hospitals NHS Foundation Trust | London | England | United Kingdom | NW1 2PG |
| 14 | Sarah Cannon Cancer Center | London | England | United Kingdom | W1G 6AD |
| 15 | The Christie NHS Foundation Trust | Manchester | England | United Kingdom | M20 4BX |
| 16 | The Royal Marsden NHS Foundation Trust | Sutton | United Kingdom | SM2 5PT |
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:
NCT02552121
Other Study ID Numbers:
- GEN702
- innovaTV 202
First Posted:
Sep 16, 2015
Last Update Posted:
Apr 8, 2021
Last Verified:
Mar 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Keywords provided by Seagen Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | For the Dose Escalation, participants took part in the trial at 3 sites located in Denmark, the United Kingdom (UK), and the United States (USA) from 30 Nov 2015 until 10 Feb 2017. Cohort Expansion trial was performed at 10 sites located in Belgium, UK, Denmark, and the USA from 16 Feb 2016 until the last participant visit on 13 Dec 2017. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Period Title: Part 1: Dose Level 1 (Weeks 1-16) | ||||||||
| STARTED | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Part 1: Dose Level 1 (Weeks 1-16) | ||||||||
| STARTED | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Part 1: Dose Level 1 (Weeks 1-16) | ||||||||
| STARTED | 0 | 0 | 11 | 3 | 1 | 5 | 1 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 11 | 3 | 1 | 4 | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Total of all reporting groups |
| Overall Participants | 3 | 6 | 11 | 3 | 1 | 5 | 1 | 3 | 33 |
| Age, Customized (Count of Participants) | |||||||||
| Adults (18-64 years) |
0
0%
|
3
50%
|
10
90.9%
|
3
100%
|
1
100%
|
4
80%
|
1
100%
|
3
100%
|
25
75.8%
|
| From 65 to 84 years |
3
100%
|
3
50%
|
1
9.1%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
0
0%
|
8
24.2%
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
1
33.3%
|
4
66.7%
|
11
100%
|
3
100%
|
1
100%
|
5
100%
|
1
100%
|
3
100%
|
29
87.9%
|
| Male |
2
66.7%
|
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
12.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3%
|
| Not Hispanic or Latino |
3
100%
|
6
100%
|
10
90.9%
|
3
100%
|
1
100%
|
5
100%
|
1
100%
|
3
100%
|
32
97%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
16.7%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
6.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
5
83.3%
|
10
90.9%
|
3
100%
|
1
100%
|
5
100%
|
1
100%
|
3
100%
|
31
93.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||||||
| Belgium |
0
0%
|
0
0%
|
6
54.5%
|
3
100%
|
0
0%
|
2
40%
|
0
0%
|
2
66.7%
|
13
39.4%
|
| United States |
0
0%
|
3
50%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
12.1%
|
| Denmark |
2
66.7%
|
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
0
0%
|
5
15.2%
|
| United Kingdom |
1
33.3%
|
1
16.7%
|
4
36.4%
|
0
0%
|
1
100%
|
2
40%
|
1
100%
|
1
33.3%
|
11
33.3%
|
| Weight (kg) [Median (Full Range) ] | |||||||||
| Part 1: Dose Escalation |
80.0
|
67.5
|
74.7
|
||||||
| Part 2: Cohort Expansion |
66.8
|
55.2
|
57.8
|
72.0
|
96.8
|
65.3
|
64.8
|
||
| Height (cm) [Median (Full Range) ] | |||||||||
| Part 1: Dose Escalation |
171.0
|
162.0
|
168.0
|
||||||
| Part 2: Cohort Expansion |
159.0
|
157.0
|
160.6
|
168.0
|
170.5
|
161.0
|
160.8
|
||
| Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ] | |||||||||
| Part 1: Dose Escalation |
27.4
|
25.5
|
25.7
|
||||||
| Part 2: Cohort Expansion |
26.4
|
22.4
|
22.4
|
24.0
|
33.3
|
24.9
|
25.1
|
||
Outcome Measures
| Title | Part 1: Number of Participants Who Experience at Least One Adverse Event (AE) |
|---|---|
| Description | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
3
100%
|
6
100%
|
| Title | Part 2: Number of Participants Who Experience at Least One Adverse Event (AE) |
|---|---|
| Description | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
11
366.7%
|
3
50%
|
1
9.1%
|
5
166.7%
|
0
0%
|
3
60%
|
| Title | Part 1: Number of Participants Who Experienced at Least One or More Serious Adverse Event (SAE) |
|---|---|
| Description | A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
1
33.3%
|
2
33.3%
|
| Title | Part 2: Number of Participants Reporting One or More Serious Adverse Events (SAE) |
|---|---|
| Description | A SAE is defined as an AE that met one or more of the following criteria/outcomes which were classified as serious: Required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. Was a congenital anomaly/birth defect. Medically important determined by the investigator. Resulted in death. Was life-threatening. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
9
300%
|
2
33.3%
|
0
0%
|
2
66.7%
|
0
0%
|
1
20%
|
| Title | Part 1: Number of Participants Reporting One or More Infusion-related Adverse Events |
|---|---|
| Description | An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator. |
| Time Frame | Day 1, Day 8 & Day 15 (+1 day) until end of treatment (Part 1), approximately 48 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
2
66.7%
|
4
66.7%
|
| Title | Part 2: Number of Participants Reporting One or More Infusion-related Adverse Events |
|---|---|
| Description | An infusion-related adverse event (AE) was defined as an AE occurring during infusion where the onset date and time of the event occurred within infusion time (+24 hours), and the event was judged as related to tisotumab vedotin by the investigator. |
| Time Frame | Day 1, Day 8 & Day 15 (+1 day) until end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
4
133.3%
|
2
33.3%
|
1
9.1%
|
1
33.3%
|
0
0%
|
1
20%
|
| Title | Part 1: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events |
|---|---|
| Description | A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
1
33.3%
|
3
50%
|
| Title | Part 2: Number of Participants Reporting One or More Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3 Adverse Events |
|---|---|
| Description | A CTCAE AE was determined using the CTCAE grading systems based on NCI-CTCAE version 4.03 assessed by the investigator. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
10
333.3%
|
2
33.3%
|
0
0%
|
3
100%
|
0
0%
|
1
20%
|
| Title | Part 1: Number of Participants Reporting One or More Treatment-related Adverse Events |
|---|---|
| Description | A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
3
100%
|
6
100%
|
| Title | Part 2: Number of Participants Reporting One or More Treatment-related Adverse Events |
|---|---|
| Description | A treatment-related AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; which has a causal relationship with the treatment. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
9
300%
|
3
50%
|
1
9.1%
|
5
166.7%
|
0
0%
|
3
60%
|
| Title | Part 1: Number of Participants With Markedly Abnormal Laboratory Values |
|---|---|
| Description | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade >=3 laboratory abnormality events. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
0
0%
|
6
100%
|
| Title | Part 2: Number of Participants With Markedly Abnormal Laboratory Values |
|---|---|
| Description | The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Markedly abnormal laboratory values are defined as any grade >=3 laboratory abnormality events. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
5
166.7%
|
2
33.3%
|
0
0%
|
3
100%
|
1
100%
|
3
60%
|
| Title | Part 1: Number of Participants Who Experienced a Skin Rash |
|---|---|
| Description | |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
0
0%
|
4
66.7%
|
| Title | Part 2: Number of Participants Who Experienced a Skin Rash |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
2
66.7%
|
0
0%
|
1
9.1%
|
1
33.3%
|
0
0%
|
1
20%
|
| Title | Part 1: Number of Participants Who Experienced a Bleeding Event |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 1), up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
3
100%
|
5
83.3%
|
| Title | Part 2: Number of Participants Who Experienced a Bleeding Event |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
7
233.3%
|
3
50%
|
1
9.1%
|
5
166.7%
|
0
0%
|
2
40%
|
| Title | Part 1: Number of Participants Who Experienced a Neuropathy Event |
|---|---|
| Description | |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
1
33.3%
|
3
50%
|
| Title | Part 2: Number of Participants Who Experienced a Neuropathy Event |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
3
100%
|
1
16.7%
|
0
0%
|
2
66.7%
|
0
0%
|
1
20%
|
| Title | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), + 24 hours 3rd infusion (Day 16), + 72 hours 3rd infusion (Day 18), + 168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
3336
(7.3)
|
5317
(34.6)
|
| Cycle 1 Day 1 |
867
(17.6)
|
1328
(48.0)
|
| Cycle 1 Day 8 |
1603
(16.2)
|
2216
(11.7)
|
| Cycle 1 Day 15 |
789
(15.6)
|
1411
(94.2)
|
| Title | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
2267
(24.8)
|
1755
(19.1)
|
||||
| Cycle 1 Dose 1 |
1889
(29.3)
|
1412
(11.9)
|
||||
| Cycle 1 Dose 2 |
150
(56.2)
|
123
(85.4)
|
||||
| Cycle 1 Dose 3 |
410
(26.4)
|
204
(71.3)
|
| Title | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8 and 15, + 24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL] |
920
(3.6)
|
1106
(21.3)
|
| Title | Part 1: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
21.2
(14.5)
|
30.7
(10.1)
|
| Cycle 1 Day 1 |
20.2
(17.9)
|
28.7
(12.1)
|
| Cycle 1 Day 8 |
20.9
(14.1)
|
28.0
(8.9)
|
| Cycle 1 Day 15 |
19.9
(11.8)
|
26.8
(21.6)
|
| Title | Part 2: Cmax: Maximum Observed Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
28.2
(34.5)
|
19.5
(17.6)
|
||||
| Cycle 1 Dose 1 |
28.2
(34.5)
|
19.5
(17.6)
|
||||
| Cycle 1 Dose 2 |
1.00
(42.0)
|
1.13
(112.2)
|
||||
| Cycle 1 Dose 3 |
3.85
(24.5)
|
1.85
(77.6)
|
| Title | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
5.864
(172.022)
|
5.061
(166.177)
|
| Cycle 1 Day 1 |
0.747
(11.547)
|
0.873
(79.228)
|
| Cycle 1 Day 8 |
0.717
(0.000)
|
0.846
(86.481)
|
| Cycle 1 Day 15 |
1.141
(81.075)
|
1.084
(73.110)
|
| Title | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
0.75
(68.49)
|
0.58
(22.85)
|
||||
| Cycle 1 Dose 1 |
0.75
(68.49)
|
0.58
(22.85)
|
||||
| Cycle 1 Dose 2 |
165.06
(75.01)
|
106.93
(55.38)
|
||||
| Cycle 1 Dose 3 |
71.23
(24.35)
|
80.37
(20.24)
|
| Title | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Time Frame | Before infusion of Day 1, 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 Day 1 |
30.0
(0)
|
30.0
(0)
|
| Cycle 1 Day 8 |
797.3
(22.1)
|
1328.5
(191.8)
|
| Cycle 1 Day 15 |
912.1
(23.7)
|
989.0
(44.3)
|
| Title | Part 1: Terminal Phase Elimination Half-life (T1/2) for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
40.45
(24.78)
|
48.15
(16.47)
|
| Title | Part 1: Total Clearance (CL) of Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate pharmacokinetic samples were collected after the third dose to define a terminal phase, and therefore CL could not be determined. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/h/kg] |
0.979
(3.561)
|
1.085
(21.476)
|
| Title | Part 1: Apparent Volume of Distribution (Vz) for Tisotumab Vedotin (HuMax-TF-ADC) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore Vz could not be determined. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/kg] |
66.75
(6.67)
|
75.37
(14.89)
|
| Title | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
3916
(7.3)
|
5573
(15.0)
|
| Cycle 1 Day 1 |
1058
(15.0)
|
1530
(34.7)
|
| Cycle 1 Day 8 |
1750
(16.2)
|
2460
(8.5)
|
| Cycle 1 Day 15 |
1012
(25.7)
|
1426
(28.6)
|
| Title | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
2660
(20.0)
|
1948
(35.2)
|
||||
| Cycle 1 Dose 1 |
1980
(24.5)
|
460
(84.5)
|
||||
| Cycle 1 Dose 2 |
299
(55.0)
|
192
(80.9)
|
||||
| Cycle 1 Dose 3 |
679
(25.7)
|
291
(89.9)
|
| Title | Part 1: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [h*µg/mL] |
1268
(14.4)
|
1594
(24.6)
|
| Title | Part 1: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
22.1
(9.1)
|
31.7
(11.9)
|
| Cycle 1 Day 1 |
20.3
(14.3)
|
30.2
(34.7)
|
| Cycle 1 Day 8 |
21.0
(6.3)
|
29.2
(6.6)
|
| Cycle 1 Day 15 |
20.9
(12.0)
|
29.2
(16.2)
|
| Title | Part 2: Cmax: Maximum Observed Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
27.5
(36.4)
|
20.6
(18.6)
|
||||
| Cycle 1 Dose 1 |
27.5
(36.4)
|
20.6
(18.6)
|
||||
| Cycle 1 Dose 2 |
2.00
(41.6)
|
1.91
(105.0)
|
||||
| Cycle 1 Dose 3 |
6.39
(24.6)
|
3.68
(66.1)
|
| Title | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
36.445
(99.474)
|
14.003
(117.534)
|
| Cycle 1 Day 1 |
0.747
(11.547)
|
0.893
(66.752)
|
| Cycle 1 Day 8 |
0.717
(0)
|
0.869
(78.568)
|
| Cycle 1 Day 15 |
0.727
(4.784)
|
0.896
(78.665)
|
| Title | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
0.86
(73.61)
|
0.58
(22.85)
|
||||
| Cycle 1 Dose 1 |
0.86
(73.61)
|
0.58
(22.85)
|
||||
| Cycle 1 Dose 2 |
165.06
(75.01)
|
106
(55.38)
|
||||
| Cycle 1 Dose 3 |
71.23
(24.35)
|
80.37
(20.24)
|
| Title | Part 1: Terminal Phase Elimination Half-life (T1/2) for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected after the third dose to define a terminal phase, and therefore t1/2 could not be determined. |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
49.56
(17.35)
|
49.34
(19.18)
|
| Title | Part 1 and Part 2: Total Clearance (CL) of Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | CL could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken. |
| Time Frame | 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| CL could not be estimated for Part 1 or Part 2 participants. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 1 & Part 2: Apparent Volume of Distribution (Vz) for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Vz could not be estimated for Part 1 or Part 2 participants due to insufficient number of samples taken. |
| Time Frame | 0 to 2 hours post-dose on days 1, 8, 15, +24 hrs 1st infusion, +24 hrs 3rd infusion, +72 hrs 3rd infusion, +168 hrs 3rd infusion (Part 1) and 0 to 2 hours post-dose on day 1, and pre-dose days 8 and 15 (Part 2) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Vz could not be estimated for Part 1 or Part 2 participants. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Total HuMax-TF (Conjugated and Non-conjugated) |
|---|---|
| Description | Data is only available for Part 1, for Part 2, inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Time Frame | Before infusion on Day 1, 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Data includes all randomized participants for whom data were available. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 Day 1 |
150.0
(0.0)
|
150.0
(0.0)
|
| Cycle 1 Day 8 |
1273.1
(23.4)
|
1252.2
(53.3)
|
| Cycle 1 Day 15 |
1625.1
(24.4)
|
1863.8
(46.6)
|
| Title | Part 1: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
885
(27.1)
|
968
(59.7)
|
| Cycle 1 Day 1 |
185
(48.1)
|
185
(75.3)
|
| Cycle 1 Day 8 |
180
(14.1)
|
236
(75.5)
|
| Cycle 1 Day 15 |
506
(25.3)
|
520
(51.3)
|
| Title | Part 2: AUC0-t: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration for Free Toxin (MMAE) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
920
(74.5)
|
1049
(89.4)
|
||||
| Cycle 1 Dose 1 |
439
(69.3)
|
393
(100.0)
|
||||
| Cycle 1 Dose 2 |
378
(121.3)
|
366
(77.9)
|
||||
| Cycle 1 Dose 3 |
713
(49.9)
|
494
(121.7)
|
| Title | Part 1: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
2.76
(23.7)
|
2.88
(52.4)
|
| Cycle 1 Day 1 |
1.46
(54.7)
|
1.38
(78.4)
|
| Cycle 1 Day 8 |
1.18
(19.8)
|
1.54
(75.4)
|
| Cycle 1 Day 15 |
2.76
(23.7)
|
2.88
(52.4)
|
| Title | Part 2: Cmax: Maximum Observed Plasma Concentration for Free Toxin (MMAE) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
3.9
(97.0)
|
3.6
(101.4)
|
||||
| Cycle 1 Dose 1 |
1.9
(110.5)
|
1.5
(80.4)
|
||||
| Cycle 1 Dose 2 |
2.47
(136.4)
|
2.50
(81.1)
|
||||
| Cycle 1 Dose 3 |
3.78
(81.6)
|
3.23
(125.0)
|
| Title | Part 1: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) |
|---|---|
| Description | |
| Time Frame | Before infusion, end of infusion (+15 minutes), and +2 hours post infusion on days 1, 8, and 15, +24 hours 1st infusion (Day 2), +24 hours 3rd infusion (Day 16), +72 hours 3rd infusion (Day 18), and +168 hours 3rd infusion (Day 22) of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the entire cycle. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 |
392.024
(3.256)
|
373.366
(6.290)
|
| Cycle 1 Day 1 |
44.568
(114.567)
|
32.001
(125.788)
|
| Cycle 1 Day 8 |
10.354
(165.509)
|
20.837
(106.094)
|
| Cycle 1 Day 15 |
54.511
(20.424)
|
32.537
(63.879)
|
| Title | Part 2: Tmax: Time to Reach the Maximum Plasma Concentration for Free Toxin (MMAE) |
|---|---|
| Description | Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3wk). Data has only been provided for participants who received the original dosing schedule of 3 times every 4 weeks (3q4wk). |
| Time Frame | Before infusion, end of infusion (+15 minutes) and +2 hours post infusion on day 1, and before infusion on days 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were collected for cohorts 3-6 to calculate PK parameters. Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, only Cycle 1 is reported. Cycle 1 is an overall value, calculated over the cycle. Includes data for all randomized participants for whom data were available. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 0 | 0 | 0 | 0 |
| Cycle 1 |
307.05
(36.52)
|
410.61
(3.82)
|
||||
| Cycle 1 Dose 1 |
160.56
(5.66)
|
162.19
(1.71)
|
||||
| Cycle 1 Dose 2 |
164.82
(56.71)
|
106.93
(55.38)
|
||||
| Cycle 1 Dose 3 |
78.37
(50.26)
|
80.37
(20.24)
|
| Title | Part 1: Trough Concentration (Ctrough) Steady State Plasma Pharmacokinetic for Free Toxin (MMAE) |
|---|---|
| Description | Data is only available for Part 1, for Part 2 inadequate samples were collected to fully evaluate separate PK parameters after doses 1, 2, and 3. |
| Time Frame | Before infusion on Day 1, 8 and 15 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Insufficient samples were taken in Cycle 2 and beyond to calculate PK parameters, therefore only Cycle 1 is reported. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Cycle 1 Day 1 |
12.50
(0)
|
12.50
(0)
|
| Cycle 1 Day 8 |
853.42
(22.93)
|
1061.28
(87.81)
|
| Cycle 1 Day 15 |
1013.22
(14.47)
|
1384.29
(83.43)
|
| Title | Part 1: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result |
|---|---|
| Description | |
| Time Frame | Baseline to end of follow-up; maximum follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Part 2: Number of Participants With a Positive Anti-drug Antibody (ADA) Immunogenicity Result |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Part 1: Number of Patients Who Experienced Anti-tumor Activity Measured by Tumor Shrinkage |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 1), up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Count of Participants [Participants] |
1
33.3%
|
3
50%
|
| Title | Part 2: Anti-tumor Activity Measured by Percentage of Change in Sum of Lesion Measurements |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Mean (Standard Deviation) [percentage of change] |
-17.34
(43.388)
|
32.78
(83.933)
|
-63.27
(NA)
|
0.74
(21.877)
|
0
(NA)
|
11.76
(27.658)
|
| Title | Part 1: Response Evaluation Based on PSA (Prostate Specific Antigen [Prostate Cancer]): Percentage Change From Baseline to End of Study |
|---|---|
| Description | |
| Time Frame | Baseline to end of follow-up; maximum follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| PSA is only assessed for participants with prostate cancer. 2 participants in Part 1 Cohort 1 and 1 participant in Part 1 Cohort 2 had the indication of prostate cancer. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 1 |
| Mean (Standard Deviation) [percentage of change] |
23.42
(61.686)
|
12.97
(NA)
|
| Title | Part 1: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study |
|---|---|
| Description | |
| Time Frame | Baseline to end of follow-up; maximum follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| CA 125 is only assessed for participants with ovarian and endometrial cancer, 1 participant in Cohort 1 and 1 participant in Cohort 2 had the indication of ovarian or endometrial cancer. No participants from Cohort 1 with the indication of ovarian and endometrial Cancer had results at the End of Study visit. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 0 | 1 |
| Mean (Standard Deviation) [percentage of change] |
186.21
(NA)
|
| Title | Part 2: Response Evaluation Based on CA125 (Cancer Antigen 125 [Ovarian and Endometrial Cancer]): Percentage of Change From Baseline to End of Study |
|---|---|
| Description | |
| Time Frame | Baseline to end of trial (Part 2), up to 36 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| CA 125 was only assessed for participants with Ovarian cancer. No participants from Cohort 5 participated in the End of Trial visit. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian |
|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. |
| Measure Participants | 8 | 1 | 0 |
| Mean (Standard Deviation) [percentage of change] |
-31.75
(36.235)
|
-32.50
(NA)
|
| Title | Part 1: Best Overall Response (OR) |
|---|---|
| Description | Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Time Frame | Baseline to end of trial (Part 1), up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Complete Response |
0
0%
|
0
0%
|
| Partial Response |
0
0%
|
1
16.7%
|
| Stable Disease |
2
66.7%
|
3
50%
|
| Progressive Disease |
1
33.3%
|
1
16.7%
|
| Not Evaluable |
0
0%
|
1
16.7%
|
| Title | Part 2: Best Overall Response (OR) |
|---|---|
| Description | Best OR (by investigators assessment) was the best response recorded from the start of the treatment until disease progression or death. Complete response: the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to < 10 mm. Based on non-target lesions, complete response was defined as disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial response (PR): ≥ 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LDs. Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of LDs while in trial. Based on non-target lesions, stable disease was defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response |
3
100%
|
1
16.7%
|
1
9.1%
|
2
66.7%
|
0
0%
|
0
0%
|
| Stable Disease |
3
100%
|
0
0%
|
0
0%
|
2
66.7%
|
0
0%
|
2
40%
|
| Progressive Disease |
2
66.7%
|
2
33.3%
|
0
0%
|
1
33.3%
|
1
100%
|
1
20%
|
| Not Evaluable |
3
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Part 1: Number of Participants Who Experienced Disease Control |
|---|---|
| Description | Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later. |
| Time Frame | 6, 12, 24 and 36 weeks post first infusion (Part 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 3 | 6 |
| Disease Control - Yes |
2
66.7%
|
3
50%
|
| Disease Control - No |
1
33.3%
|
3
50%
|
| Disease Control - Yes |
0
0%
|
0
0%
|
| Disease Control - No |
3
100%
|
6
100%
|
| Disease Control - Yes |
0
0%
|
0
0%
|
| Disease Control - No |
3
100%
|
6
100%
|
| Disease Control - Yes |
0
0%
|
0
0%
|
| Disease Control - No |
3
100%
|
6
100%
|
| Title | Part 2: Number of Participants Who Experienced Disease Control |
|---|---|
| Description | Participants were defined as having disease control at a specific time point if they had an evaluation of complete response (CR) or partial response (PR) at the time point (with a window of +/- 7 days) or had an evaluation of stable disease (SD), PR or CR at any point from the time point minus 7 days or later. |
| Time Frame | 6, 12, 24 and 36 weeks post first infusion (Part 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 11 | 3 | 1 | 5 | 1 | 3 |
| Disease Control - Yes |
6
200%
|
1
16.7%
|
1
9.1%
|
4
133.3%
|
0
0%
|
2
40%
|
| Disease Control - No |
5
166.7%
|
2
33.3%
|
0
0%
|
1
33.3%
|
1
100%
|
1
20%
|
| Disease Control - Yes |
2
66.7%
|
1
16.7%
|
1
9.1%
|
2
66.7%
|
0
0%
|
1
20%
|
| Disease Control - No |
9
300%
|
2
33.3%
|
0
0%
|
3
100%
|
1
100%
|
2
40%
|
| Disease Control - Yes |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
| Disease Control - No |
11
366.7%
|
3
50%
|
1
9.1%
|
4
133.3%
|
1
100%
|
3
60%
|
| Disease Control - Yes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Disease Control - No |
11
366.7%
|
3
50%
|
1
9.1%
|
5
166.7%
|
1
100%
|
3
60%
|
| Title | Part 1: Progression Free Survival (PFS) |
|---|---|
| Description | Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest. |
| Time Frame | Baseline to end of follow-up; maximum time of follow-up was 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 2 | 1 |
| Median (95% Confidence Interval) [weeks] |
11.3
|
NA
|
| Title | Part 2: Progression Free Survival (PFS) |
|---|---|
| Description | Progression-free survival was defined as the time in weeks from date of first dose until the date of disease progression or death, whichever is earliest. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity. |
| Measure Participants | 4 | 2 | 1 | 4 | 1 | 3 |
| Median (95% Confidence Interval) [weeks] |
10.7
|
8.0
|
22.0
|
14.0
|
5.0
|
11.9
|
| Title | Part 1: Duration of Response |
|---|---|
| Description | Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the date of first progressive disease (PD) or death. |
| Time Frame | Baseline to end of trial (Part 1), up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of Response could not be estimated in the Dose Escalation or the Cohort Expansion parts of the trial because patients with a confirmed response were discontinued due to toxicity or other reason different from progressive disease (PD) or death. |
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg |
|---|---|---|
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). |
| Measure Participants | 0 | 0 |
| Title | Part 2: Duration of Response |
|---|---|
| Description | Duration of response was defined as as the number of days from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) to the date of first progressive disease (PD) or death. |
| Time Frame | Baseline to end of trial (Part 2), up to 36 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Duration of Response could not be estimated in the Dose Escalation or the Cohort Expansion parts of the trial because patients with a confirmed response were discontinued due to toxicity or other reason different from progressive disease (PD) or death. |
| Arm/Group Title | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2: Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2: Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | Part 1: Dose Escalation: Baseline to follow-up; maximum time of follow-up was 24 weeks. Part 2: Cohort Expansion: Baseline to a maximum of 36 weeks. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||
| Arm/Group Title | Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | ||||||||
| Arm/Group Description | Tisotumab vedotin 0.9 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Tisotumab vedotin 1.2 mg/kg was administered as an intravenous infusion, over a minimum of 30 minutes, 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (the recommended dose for phase II trials [RP2D] from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion, once every 3 weeks (1q3w). | Participants with the indication of cervical cancer, received Tisotumab vedotin 1.2 mg/kg (RP2D from the Dose Escalation part), administered as an intravenous infusion, over a minimum of 30 minutes 3 times every 4 weeks (3q4wk). Due to severe ocular toxicity, participants switched to receive Tisotumab vedotin at 2.0 mg/kg, administered as an intravenous infusion, once every 3 weeks (1q3w). | Participants with the indication of ovarian cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | Participants with the indication of cervical cancer, received Tisotumab vedotin 2.0 mg/kg, administered as an intravenous infusion, over a minimum of 30 minutes, once every 3 weeks (1q3w); the revised dose and schedule due to severe ocular toxicity observed at 1.2 mg/kg 3q4wk. | ||||||||
All Cause Mortality |
||||||||||||||||
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | |||||||||
| 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 | 0/3 (0%) | 0/6 (0%) | 1/11 (9.1%) | 0/3 (0%) | 0/1 (0%) | 0/5 (0%) | 0/1 (0%) | 0/3 (0%) | ||||||||
Serious Adverse Events |
||||||||||||||||
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | |||||||||
| 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 | 1/3 (33.3%) | 2/6 (33.3%) | 9/11 (81.8%) | 2/3 (66.7%) | 0/1 (0%) | 2/5 (40%) | 0/1 (0%) | 1/3 (33.3%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Atrial flutter | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| Symblepharon | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 4/11 (36.4%) | 4 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Colonic pseudo-obstruction | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Nausea | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Abdominal pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Small intestinal obstruction | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| General disorders | ||||||||||||||||
| General physical health deterioration | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Disease progression | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Conjunctivitis | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 3/11 (27.3%) | 3 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Gastroenteritis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hyponatraemia | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Bone pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Vaginal haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Pneumonitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| Part 1: Dose Escalation: Cohort 1 3q4wk 0.9 mg/kg | Part 1: Dose Escalation: Cohort 2 3q4wk 1.2 mg/kg | Part 2: Cohort Expansion: Cohort 1 3q4wk Ovarian | Part 2: Cohort Expansion: Cohort 2 3q4wk Cervical | Part 2 Cohort Expansion: Cohort 3 3q4wk - 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 4 3q4wk - 1q3w Cervical | Part 2 Cohort Expansion: Cohort 5 1q3w Ovarian | Part 2: Cohort Expansion: Cohort 6 1q3w Cervical | |||||||||
| 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%) | 6/6 (100%) | 10/11 (90.9%) | 3/3 (100%) | 1/1 (100%) | 5/5 (100%) | 0/1 (0%) | 3/3 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/11 (18.2%) | 4 | 1/3 (33.3%) | 2 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 |
| Febrile neutropenia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Neutropenia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Tachycardia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| Keratitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 2/5 (40%) | 4 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Lacrimation increased | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Symblepharon | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Dry eye | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Blepharitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Eye pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Meibomianitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Punctate keratitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Episcleritis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Keratopathy | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Ocular hyperaemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Ulcerative keratitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Constipation | 0/3 (0%) | 0 | 4/6 (66.7%) | 5 | 5/11 (45.5%) | 5 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Nausea | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 5/11 (45.5%) | 6 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Abdominal pain | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 4/11 (36.4%) | 4 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 3/5 (60%) | 4 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 3/11 (27.3%) | 4 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 4/5 (80%) | 6 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 |
| Dyspepsia | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Dry mouth | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Tongue blistering | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 4/11 (36.4%) | 6 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Abdominal discomfort | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Abdominal pain upper | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Abdominal pain lower | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Haematochezia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Lip ulceration | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Melaena | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Mouth ulceration | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rectal discharge | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rectal haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| General disorders | ||||||||||||||||
| Chest pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 2 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Malaise | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Fatigue | 2/3 (66.7%) | 2 | 2/6 (33.3%) | 2 | 6/11 (54.5%) | 8 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 4/5 (80%) | 6 | 0/1 (0%) | 0 | 2/3 (66.7%) | 3 |
| Pain | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Oedema | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pyrexia | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Oedema peripheral | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Infections and infestations | ||||||||||||||||
| Conjunctivitis | 2/3 (66.7%) | 2 | 6/6 (100%) | 7 | 5/11 (45.5%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 3/5 (60%) | 8 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Escherichia vaginitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Influenza | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Oral herpes | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pneumonia | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rhinitis | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Tonsillitis | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Urinary tract infection | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 |
| Viral upper respiratory tract infection | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Infection | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Cystitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rash pustular | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Upper respiratory tract infection | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||||||
| Radiation proctitis | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Investigations | ||||||||||||||||
| Weight decreased | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Alanine aminotransferase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Aspartate aminotransferase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Vital dye staining cornea present | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Blood alkaline phosphatase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Gamma-glutamyltransferase increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| International normalised ratio increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Lymphocyte count decreased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Neutrophil count decreased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Platelet count decreased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Urine output increased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| White blood cell count decreased | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Decreased appetite | 2/3 (66.7%) | 2 | 3/6 (50%) | 4 | 5/11 (45.5%) | 5 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hypokalaemia | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Dehydration | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hyperlipidaemia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hypomagnesaemia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hyponatraemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Cell death | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hypocalcaemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hypophosphataemia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Myalgia | 1/3 (33.3%) | 1 | 5/6 (83.3%) | 9 | 3/11 (27.3%) | 3 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Arthralgia | 0/3 (0%) | 0 | 2/6 (33.3%) | 3 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Back pain | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 2/11 (18.2%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 2 |
| Muscular weakness | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Muscle spasms | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 2/5 (40%) | 2 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Bone pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Flank pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Tumour pain | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Nervous system disorders | ||||||||||||||||
| Neuropathy peripheral | 0/3 (0%) | 0 | 4/6 (66.7%) | 4 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Dizziness | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Headache | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Peripheral sensory neuropathy | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Polyneuropathy | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Insomnia | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Anxiety | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Depression | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Haematuria | 0/3 (0%) | 0 | 2/6 (33.3%) | 4 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 2/3 (66.7%) | 4 |
| Acute kidney injury | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Cystitis noninfective | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Dysuria | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pollakiuria | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Urinary incontinence | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Vaginal haemorrhage | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 0/11 (0%) | 0 | 1/3 (33.3%) | 1 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Female genital tract fistula | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Epistaxis | 3/3 (100%) | 4 | 5/6 (83.3%) | 5 | 7/11 (63.6%) | 8 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 2/3 (66.7%) | 5 |
| Cough | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 2/11 (18.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rhinorrhoea | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Sinus congestion | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Nasal congestion | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 1/1 (100%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Dyspnoea | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 2/11 (18.2%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Dysphonia | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Laryngeal haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Nasal dryness | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pulmonary haemorrhage | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Alopecia | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 5/11 (45.5%) | 5 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 3/5 (60%) | 3 | 0/1 (0%) | 0 | 2/3 (66.7%) | 2 |
| Dry skin | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Pruritus | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 1/3 (33.3%) | 1 | 1/1 (100%) | 1 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Rash | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 2 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Rash maculo-papular | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 1/3 (33.3%) | 1 |
| Erythema | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Vascular disorders | ||||||||||||||||
| Hypertension | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Lymphoedema | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hot flush | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/11 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 1/5 (20%) | 1 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
| Hypotension | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/11 (9.1%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/5 (0%) | 0 | 0/1 (0%) | 0 | 0/3 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 12 months but less than 18 months from the end of study (database lock). The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Genmab |
|---|---|
| Organization | Genmab A/S |
| Phone | 7020 2728 ext +45 |
| clinicaltrials@genmab.com |
Responsible Party:
Seagen Inc.
ClinicalTrials.gov Identifier:
NCT02552121
Other Study ID Numbers:
- GEN702
- innovaTV 202
First Posted:
Sep 16, 2015
Last Update Posted:
Apr 8, 2021
Last Verified:
Mar 1, 2021