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Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)

Sponsor
ADC Therapeutics S.A. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02588092
Collaborator
(none)
35
Enrollment
11
Locations
2
Arms
30.9
Actual Duration (Months)
3.2
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). Participants will participate in a dose-escalation phase (Part

  1. and receive ADCT-301 either weekly or once every 3 weeks.

In Part 2 of the study, participants will receive a recommended dose of ADCT-301 as determined by a Dose Escalation Steering Committee.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and pharmacokinetics of ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL).

ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication.

The study will be conducted in 2 parts: In Part 1 (dose escalation) participants will either be on weekly administration or every 3-week administration. Participants on weekly administration will receive an infusion of ADCT-301 on Days 1, 8, and 15 of each 3 week treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-301 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.

In Part 2 (expansion), participants will be assigned to receive a recommended dose and/or schedule of ADCT-301 as determined by a Dose Escalation Steering Committee.

For each participant, the study will include a screening period (up to 28 days), a treatment period, and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall participant tolerability to the study drug and response to treatment. It is anticipated that the entire study (Parts 1 and 2) will enroll a maximum of 80 participants and could last approximately 3 years from first participant treated to last participant completed.

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label, Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Activity of ADCT 301 in Patients With Relapsed or Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia
Actual Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Aug 29, 2018
Actual Study Completion Date :
Aug 29, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: ADCT-301 (dose escalation)

Weekly administration - Participants will receive an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle. 3-week administration - Participants will receive an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle. The dose escalation will be conducted according to a 3+3 design.

Drug: ADCT-301
Intravenous infusion
Other Names:
  • Camidanlumab tesirine

    		•
    Experimental: Part 2: ADCT-301 (dose expansion)

    Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee.

    Drug: ADCT-301
    Intravenous infusion
    Other Names:
  • Camidanlumab tesirine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) [Day 1 to Day 21 (Cycle 1)]

      A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: - Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with <5% blasts). In case of a normocellular bone marrow with <5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: Grade 4 tumor lysis syndrome. Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). CTCAE Grade 3 or higher skin ulceration. Peripheral sensory or motor neuropathy ≥ Grade 2.

    2. Recommended Dose of ADCT-301 for Part 2 [Day 1 to Day 21 (Cycle 1)]

      The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.

    3. Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) [Day 1 to a maximum of 24 weeks (+ 30 days)]

      A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

    4. Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) [Day 1 to a maximum of 24 weeks (+ 30 days)]

      An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.

    Secondary Outcome Measures

    1. Duration of Response (DOR) [Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)]

      DOR is defined among responders (complete response [CR], CR with incomplete blood count recover [CRi], or partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. CR: Bone marrow differential showing ≤5% blast cells. Absolute neutrophil count (ANC) ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L. Absence of extramedullary disease. Participant is independent of red blood cell transfusions. CRi is defined as achieving all CR criteria except that values for ANC may be <1.0 x 10^9/L and/or values for platelets may be <100 x 10^9/L. PR: ANC ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L. Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level >5% and ≤25%, or bone marrow differential showing <5% blast cells.

    2. Overall Response Rate (ORR) [Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)]

      ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders.

    3. Overall Survival (OS) [Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)]

      OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.

    4. Number of Participants With Progression Free Survival (PFS) [Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)]

      PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.

    5. Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts.

    6. Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    7. Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    8. Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    9. Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    10. Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    11. Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    12. Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    13. Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    14. Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    15. Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.

    16. Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1.

    17. Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    18. Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    19. Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    20. Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    21. Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    22. Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    23. Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    24. Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    25. Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule [Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)]

      CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.

    26. Clearance (CL) for ADCT-301 for the QW Dosing Schedule [Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)]

      CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.

    27. Number of Participants With Anti-drug Antibody Response (Against ADCT-301) [Day 1 to the end of Cycle 2 (6 weeks)]

      Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Relapsed or refractory CD25-positive AML [per World Health Organization (WHO)].

    • Relapsed or refractory CD25-positive ALL [per World Health Organization (WHO)].

    • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

    • Creatinine ≤1.5mg/dL.

    • Serum/plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement.

    • Total serum/plasma bilirubin ≤1.5 times the upper limit of normal.

    • Women of childbearing potential must have a negative urine or serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1.

    • Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception.

    • White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.

    Exclusion Criteria:

    • Participants who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease.

    • Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening.

    • Active graft versus host disease.

    • Autologous or allogenic transplant within the 60 days prior to Screening.

    • Known history of immunogenicity or hypersensitivity to a CD25 antibody.

    • Known history of positive serum human anti-drug antibodies (ADA), or known allergy to any component of ADCT-301.

    • Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy.

    • History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.

    • Pregnant or breastfeeding women.

    • Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias.

    • Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case < 14 days prior to the start of the study treatment on Cycle 1, Day 1.

    • Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted therapies within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor.

    • Failure to recover (to CTCAE Version 4.0 Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.

    • Isolated extramedullary relapse (i.e., testicular, CNS).

    • Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening (unless secondary to pacemaker or bundle branch block).

    • Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy.

    • Any other significant medical illness, abnormality, or condition.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Winship Cancer Institute, Emory University Atlanta Georgia United States 30322
    2 Northside Hospital Atlanta Georgia United States 30342
    3 The University of Chicago Medical Center Chicago Illinois United States 60647
    4 Memorial Sloan Kettering Cancer Center New York New York United States
    5 Duke Cancer Center Durham North Carolina United States 27710
    6 Greenville Health System, Institute for Translational Oncology Research Greenville South Carolina United States 29605
    7 The University of Texas M.D. Anderson Cancer Center Houston Texas United States 77030
    8 Virginia Cancer Specialists, PC Fairfax Virginia United States 22031
    9 Swedish Cancer Institute Seattle Washington United States 98104
    10 University of Washington Medical Center Seattle Washington United States 98109
    11 Froedtert Hospital/ Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • ADC Therapeutics S.A.

    Investigators

    • Principal Investigator: Aaron Goldberg, MD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    ADC Therapeutics S.A.
    ClinicalTrials.gov Identifier:
    NCT02588092
    Other Study ID Numbers:
    • ADCT-301-002
    First Posted:
    Oct 27, 2015
    Last Update Posted:
    Feb 26, 2020
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by ADC Therapeutics S.A.
    Camidanlumab tesirine
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Leukemia, Lymphoid

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at 11 sites in the United States between 01 February 2016 and 29 August 2018.
    Pre-assignment Detail
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle. Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Period Title: Overall Study
    STARTED 4 3 3 3 3 3 3 4 6 3
    COMPLETED 0 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 4 3 3 3 3 3 3 4 6 3

    Baseline Characteristics

    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW Total
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Total of all reporting groups
    Overall Participants 4 3 3 3 3 3 3 4 6 3 35
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    2
    50%
    0
    0%
    2
    66.7%
    2
    66.7%
    0
    0%
    1
    33.3%
    0
    0%
    2
    50%
    1
    16.7%
    2
    66.7%
    12
    34.3%
    >=65 years
    2
    50%
    3
    100%
    1
    33.3%
    1
    33.3%
    3
    100%
    2
    66.7%
    3
    100%
    2
    50%
    5
    83.3%
    1
    33.3%
    23
    65.7%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    66.8
    (11.09)
    72.3
    (4.73)
    51.0
    (17.78)
    51.7
    (26.27)
    69.3
    (2.89)
    67.0
    (13.00)
    75.7
    (5.69)
    56.5
    (18.43)
    71.0
    (10.77)
    63.3
    (10.02)
    64.9
    (14.21)
    Sex: Female, Male (Count of Participants)
    Female
    1
    25%
    1
    33.3%
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    1
    25%
    3
    50%
    0
    0%
    10
    28.6%
    Male
    3
    75%
    2
    66.7%
    3
    100%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    2
    66.7%
    3
    75%
    3
    50%
    3
    100%
    25
    71.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.9%
    Not Hispanic or Latino
    4
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    2
    66.7%
    3
    100%
    4
    100%
    6
    100%
    3
    100%
    34
    97.1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    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%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    4
    100%
    3
    100%
    2
    66.7%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    75%
    6
    100%
    3
    100%
    33
    94.3%
    More than one race
    0
    0%
    0
    0%
    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%
    1
    25%
    0
    0%
    0
    0%
    1
    2.9%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    4
    100%
    6
    100%
    3
    100%
    35
    100%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    169.40
    (10.641)
    179.27
    (15.255)
    183.20
    (9.354)
    170.00
    (4.359)
    176.33
    (4.856)
    165.50
    (18.007)
    168.57
    (6.562)
    169.38
    (11.762)
    169.52
    (12.478)
    177.22
    (3.586)
    172.44
    (10.774)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    94.98
    (24.758)
    99.30
    (12.644)
    73.50
    (7.988)
    72.20
    (11.722)
    105.67
    (24.509)
    71.63
    (15.053)
    71.67
    (11.395)
    79.45
    (17.436)
    74.10
    (5.686)
    75.23
    (5.200)
    81.43
    (17.597)
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    29.37
    (3.100)
    31.09
    (4.209)
    21.94
    (2.469)
    24.89
    (3.002)
    33.86
    (7.003)
    25.98
    (1.259)
    25.52
    (6.243)
    27.47
    (3.759)
    26.03
    (3.607)
    23.94
    (0.934)
    26.94
    (4.656)
    Eastern Cooperative Oncology Group (ECOG) performance status (Count of Participants)
    0
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.9%
    1
    3
    75%
    3
    100%
    2
    66.7%
    2
    66.7%
    3
    100%
    2
    66.7%
    2
    66.7%
    3
    75%
    5
    83.3%
    2
    66.7%
    27
    77.1%
    2
    1
    25%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    25%
    1
    16.7%
    1
    33.3%
    7
    20%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
    Description A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: - Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with <5% blasts). In case of a normocellular bone marrow with <5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: Grade 4 tumor lysis syndrome. Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). CTCAE Grade 3 or higher skin ulceration. Peripheral sensory or motor neuropathy ≥ Grade 2.
    Time Frame Day 1 to Day 21 (Cycle 1)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 4 3 3 3 3 3 3 4 6 3
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    2. Primary Outcome
    Title Recommended Dose of ADCT-301 for Part 2
    Description The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.
    Time Frame Day 1 to Day 21 (Cycle 1)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Part 1: ADCT-301 Dose Escalation
    Arm/Group Description Weekly administration: Participants received an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle. 3-week administration: Participants received an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle. The dose escalation was conducted according to a 3+3 design.
    Measure Participants 0
    3. Primary Outcome
    Title Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
    Description A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
    Time Frame Day 1 to a maximum of 24 weeks (+ 30 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 4 3 3 3 3 3 3 4 6 3
    Count of Participants [Participants]
    4
    100%
    2
    66.7%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    4
    100%
    6
    100%
    3
    100%
    4. Primary Outcome
    Title Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)
    Description An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.
    Time Frame Day 1 to a maximum of 24 weeks (+ 30 days)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 4 3 3 3 3 3 3 4 6 3
    Count of Participants [Participants]
    2
    50%
    1
    33.3%
    2
    66.7%
    3
    100%
    1
    33.3%
    2
    66.7%
    2
    66.7%
    2
    50%
    5
    83.3%
    3
    100%
    5. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR is defined among responders (complete response [CR], CR with incomplete blood count recover [CRi], or partial response [PR]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. CR: Bone marrow differential showing ≤5% blast cells. Absolute neutrophil count (ANC) ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L. Absence of extramedullary disease. Participant is independent of red blood cell transfusions. CRi is defined as achieving all CR criteria except that values for ANC may be <1.0 x 10^9/L and/or values for platelets may be <100 x 10^9/L. PR: ANC ≥1.0 x 10^9/L and platelet count ≥100 x 10^9/L. Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level >5% and ≤25%, or bone marrow differential showing <5% blast cells.
    Time Frame Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0 0 0 0 0 0 0 0 0
    6. Secondary Outcome
    Title Overall Response Rate (ORR)
    Description ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders.
    Time Frame Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0 0 0 0 0 0 0 0 0
    7. Secondary Outcome
    Title Overall Survival (OS)
    Description OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
    Time Frame Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0 0 0 0 0 0 0 0 0
    8. Secondary Outcome
    Title Number of Participants With Progression Free Survival (PFS)
    Description PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
    Time Frame Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0 0 0 0 0 0 0 0 0
    9. Secondary Outcome
    Title Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
    Description Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 2 1 3 3 3 3 4
    PBD-conjugated Ab of ADCT-301: Cycle 1
    181
    (348)
    165
    (NA)
    186
    (117)
    514
    (127)
    920
    (71.2)
    877
    (35.4)
    949
    (63.8)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    79.2
    (0.268)
    589
    (NA)
    405
    (383)
    284
    (102)
    1182
    (167)
    710
    (41.6)
    Total Ab of ADCT-301: Cycle 1
    278
    (355)
    177
    (NA)
    233
    (93.8)
    715
    (139)
    960
    (82.5)
    1013
    (34.4)
    1196
    (69.3)
    Total Ab of ADCT-301: Cycle 2
    91.4
    (17.0)
    272
    (236)
    517
    (330)
    333
    (121)
    1406
    (199)
    910
    (41.0)
    SG3199 Free Warhead of ADCT-301: Cycle 1
    0.0210
    (NA)
    0.0140
    (NA)
    0.0280
    (54.3)
    SG3199 Free Warhead of ADCT-301: Cycle 2
    0.0140
    (29.7)
    0.0170
    (NA)
    10. Secondary Outcome
    Title Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
    Description Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 5 2
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1
    377
    (67.0)
    355
    (39.4)
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2
    350
    (32.8)
    13200
    (NA)
    Total Ab of ADCT-301: Cycle 1 Week 1
    435
    (63.5)
    504
    (22.2)
    Total Ab of ADCT-301: Cycle 1 Week 2
    416
    (33.8)
    15100
    (NA)
    11. Secondary Outcome
    Title Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
    Description Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 2 1 3 3 3 3 4
    PBD-conjugated Ab of ADCT-301: Cycle 1
    0.162
    (34.6)
    0.0870
    (NA)
    0.0830
    (3.01)
    0.0850
    (23.4)
    0.0910
    (5.00)
    0.108
    (20.1)
    0.108
    (20.1)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    0.144
    (21.7)
    0.0490
    (NA)
    0.0620
    (33.9)
    0.0860
    (2.45)
    0.0840
    (63.1)
    0.0810
    (45.1)
    Total Ab of ADCT-301: Cycle 1
    0.162
    (34.6)
    0.0870
    (NA)
    0.0830
    (3.01)
    0.101
    (11.7)
    0.0910
    (5.00)
    0.119
    (31.2)
    0.108
    (20.1)
    Total Ab of ADCT-301: Cycle 2
    0.103
    (27.2)
    0.0490
    (NA)
    0.0770
    (17.1)
    0.123
    (50.2)
    0.0840
    (63.1)
    0.0760
    (59.1)
    SG3199 Free Warhead of ADCT-301: Cycle 1
    0.310
    (NA)
    0.379
    (NA)
    0.164
    (36.1)
    SG3199 Free Warhead of ADCT-301: Cycle 2
    0.228
    (12.8)
    0.309
    (NA)
    12. Secondary Outcome
    Title Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
    Description Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 5 2
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1
    0.0680
    (19.9)
    0.119
    (173)
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2
    0.0370
    (50.4)
    0.0240
    (NA)
    Total Ab of ADCT-301: Cycle 1 Week 1
    0.117
    (185)
    0.0590
    (18.1)
    Total Ab of ADCT-301: Cycle 1 Week 2
    0.0370
    (50.4)
    0.0240
    (NA)
    13. Secondary Outcome
    Title Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule
    Description AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 2 1 3 3 3 3 4
    PBD-conjugated Ab of ADCT-301: Cycle 1
    19.0
    (681)
    109
    (NA)
    34.9
    (363)
    317
    (43.3)
    897
    (67.5)
    1198
    (82.1)
    381
    (126)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    19.1
    (7.42)
    30.4
    (NA)
    231
    (1225)
    114
    (332)
    1063
    (135)
    360
    (180)
    Total Ab of ADCT-301: Cycle 1
    36.3
    (245)
    132
    (NA)
    46.4
    (353)
    590
    (40.6)
    1144
    (66.7)
    1577
    (69.6)
    394
    (174)
    Total Ab of ADCT-301: Cycle 2
    22.6
    (23.9)
    22.6
    (77.7)
    348
    (1389)
    127
    (452)
    1427
    (180)
    436
    (178)
    SG3199 Free Warhead of ADCT-301: Cycle 1
    0.00500
    (NA)
    0.0120
    (NA)
    0.0500
    (81.2)
    SG3199 Free Warhead of ADCT-301: Cycle 2
    0.00600
    (110)
    0.01540
    (NA)
    14. Secondary Outcome
    Title Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule
    Description AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 5 2
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1
    331
    (114)
    113
    (86.8)
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2
    378
    (103)
    2319
    (NA)
    Total Ab of ADCT-301: Cycle 1 Week 1
    476
    (116)
    152
    (103)
    Total Ab of ADCT-301: Cycle 1 Week 2
    584
    (86.8)
    3099
    (NA)
    15. Secondary Outcome
    Title Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule
    Description AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 2 2 3
    PBD-conjugated Ab of ADCT-301: Cycle 2
    1061
    (72.3)
    186
    (240)
    1248
    (114)
    826
    (151)
    Total Ab of ADCT-301: Cycle 2
    1700
    (89.6)
    60.2
    (NA)
    1751
    (146)
    622
    (167)
    16. Secondary Outcome
    Title Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule
    Description AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    The analysis was planned, but the data was not collected as study was terminated prematurely.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0
    17. Secondary Outcome
    Title Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
    Description AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 1 1 2
    PBD-conjugated Ab of ADCT-301: Cycle 1
    2846
    (NA)
    440
    (139)
    Total Ab of ADCT-301: Cycle 1
    667
    (56.3)
    1631
    (NA)
    3434
    (NA)
    1019
    (NA)
    18. Secondary Outcome
    Title Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
    Description AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 1 0
    Total Ab of ADCT-301: Cycle 1 Week 1
    366
    (NA)
    19. Secondary Outcome
    Title Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
    Description AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 2 2 3
    PBD-conjugated Ab of ADCT-301: Cycle 2
    1.00
    (0.373)
    1.00
    (0)
    1.00
    (0.0434)
    1.00
    (NA)
    Total Ab of ADCT-301: Cycle 2
    1.00
    (0.416)
    1.00
    (NA)
    1.00
    (0.113)
    1.00
    (0.000222)
    20. Secondary Outcome
    Title Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
    Description AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 4 1
    PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2
    1.13
    (9.77)
    1.00
    (NA)
    Total Ab of ADCT-301: Cycle 1 Week 2
    1.12
    (14.3)
    1.00
    (NA)
    21. Secondary Outcome
    Title Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
    Description Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 2 2 3
    PBD-conjugated Ab of ADCT-301: Cycle 1
    4.27
    (NA)
    7.34
    (120)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    6.46
    (13.9)
    7.58
    (168)
    5.94
    (25.7)
    5.29
    (NA)
    Total Ab of ADCT-301: Cycle 1
    5.69
    (28.9)
    7.04
    (NA)
    4.54
    (NA)
    3.88
    (NA)
    Total Ab of ADCT-301: Cycle 2
    5.74
    (2.99)
    6.22
    (43.3)
    7.83
    (37.1)
    22. Secondary Outcome
    Title Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
    Description Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 1 0
    Total Ab of ADCT-301: Cycle 1 Week 1
    6.07
    (NA)
    23. Secondary Outcome
    Title Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
    Description MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    This analysis was planned, but data was not collected as the study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 0 0 0 0
    24. Secondary Outcome
    Title Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
    Description MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    This analysis was planned, but data was not collected as the study was terminated prematurely.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0
    25. Secondary Outcome
    Title Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
    Description λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    This analysis was planned, but data was not collected as the study was terminated prematurely.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 0 0 0 0
    26. Secondary Outcome
    Title Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
    Description λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    This analysis was planned, but data was not collected as the study was terminated prematurely.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 0 0
    27. Secondary Outcome
    Title Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
    Description Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 2 2 3
    PBD-conjugated Ab of ADCT-301: Cycle 1
    2.28
    (NA)
    0.446
    (45.6)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    1.80
    (67.7)
    0.379
    (63.9)
    1.36
    (56.0)
    1.02
    (NA)
    Total Ab of ADCT-301: Cycle 1
    0.995
    (45.8)
    2.28
    (NA)
    2.18
    (NA)
    0.587
    (NA)
    Total Ab of ADCT-301: Cycle 2
    1.96
    (55.8)
    1.57
    (55.5)
    0.451
    (111)
    28. Secondary Outcome
    Title Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
    Description Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 1 0
    Total Ab of ADCT-301: Cycle 1 Week 1
    0.719
    (NA)
    29. Secondary Outcome
    Title Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
    Description CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
    Time Frame Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W).
    Measure Participants 0 0 0 0 2 2 2 3
    PBD-conjugated Ab of ADCT-301: Cycle 1
    1.67
    (NA)
    12.5
    (237)
    PBD-conjugated Ab of ADCT-301: Cycle 2
    2.68
    (40.6)
    14.5
    (423)
    3.28
    (84.1)
    8.20
    (163)
    Total Ab of ADCT-301: Cycle 1
    4.22
    (86.9)
    2.21
    (NA)
    1.75
    (NA)
    5.36
    (NA)
    Total Ab of ADCT-301: Cycle 2
    2.12
    (54.5)
    2.96
    (109)
    12.6
    (151)
    30. Secondary Outcome
    Title Clearance (CL) for ADCT-301 for the QW Dosing Schedule
    Description CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
    Time Frame Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
    Arm/Group Title Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    Measure Participants 1 0
    Total Ab of ADCT-301: Cycle 1 Week 1
    6.59
    (NA)
    31. Secondary Outcome
    Title Number of Participants With Anti-drug Antibody Response (Against ADCT-301)
    Description Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol.
    Time Frame Day 1 to the end of Cycle 2 (6 weeks)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Part 1: ADCT-301 Dose Escalation
    Arm/Group Description Weekly administration: Participants received an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle. 3-week administration: Participants received an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle.
    Measure Participants 34
    Count of Participants [Participants]
    2
    50%

    Adverse Events

    Time Frame Day 1 to a maximum of 24 weeks (+ 30 days)
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Arm/Group Description Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle. Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly [QW]) of each 3-week (21 day) cycle.
    All Cause Mortality
    Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 2/3 (66.7%) 2/3 (66.7%) 2/3 (66.7%) 1/4 (25%) 5/6 (83.3%) 2/3 (66.7%)
    Serious Adverse Events
    Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/4 (50%) 1/3 (33.3%) 2/3 (66.7%) 3/3 (100%) 1/3 (33.3%) 2/3 (66.7%) 2/3 (66.7%) 2/4 (50%) 5/6 (83.3%) 3/3 (100%)
    Blood and lymphatic system disorders
    Febrile Neutropenia 0/4 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 2 0/4 (0%) 0 2/6 (33.3%) 2 2/3 (66.7%) 3
    Cardiac disorders
    Atrial Fibrillation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Cardiac Arrest 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Pericarditis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Supraventricular Tachycardia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/6 (0%) 0 0/3 (0%) 0
    Gastrointestinal disorders
    Abdominal Pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1
    Intra-abdominal Haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Stomatitis 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    General disorders
    Disease Progression 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1
    Non-cardiac Chest Pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Pyrexia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Infections and infestations
    Lung Infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Pneumonia 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 2/6 (33.3%) 2 0/3 (0%) 0
    Streptococcal Bacteraemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Urinary Tract Infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Urinary Tract Infection Enterococcal 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Injury, poisoning and procedural complications
    Subdural Haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1
    Metabolism and nutrition disorders
    Decreased Appetite 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1
    Failure to Thrive 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 2
    Hyperglycaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Back Pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Lymphocytic Leukaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Acute Myeloid Leukaemia 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/4 (0%) 0 1/6 (16.7%) 1 1/3 (33.3%) 1
    Nervous system disorders
    Subarachnoid Haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1
    Psychiatric disorders
    Anxiety 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Renal and urinary disorders
    Haematuria 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 0/6 (0%) 0 0/3 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash Maculo-papular 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 2/6 (33.3%) 2 0/3 (0%) 0
    Vascular disorders
    Hypotension 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 0/6 (0%) 0 0/3 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort 1: 3 μg/kg Q3W Cohort 2: 6 μg/kg Q3W Cohort 3: 12 μg/kg Q3W Cohort 4: 22 μg/kg Q3W Cohort 5: 32 μg/kg Q3W Cohort 6: 52 μg/kg Q3W Cohort 7: 72 μg/kg Q3W Cohort 8: 92 μg/kg Q3W Cohort 9: 30 μg/kg QW Cohort 10: 37.5 μg/kg QW
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 2/3 (66.7%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 4/4 (100%) 6/6 (100%) 3/3 (100%)
    Blood and lymphatic system disorders
    Febrile Neutropenia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Anaemia 0/4 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 2/6 (33.3%) 1/3 (33.3%)
    Lymphopenia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 2/6 (33.3%) 2/3 (66.7%)
    Thrombocytopenia 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Leukocytosis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Leukopenia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 0/6 (0%) 1/3 (33.3%)
    Neutropenia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Lymphocytosis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Cardiac disorders
    Palpitations 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1/6 (16.7%) 0/3 (0%)
    Tachycardia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Angina Pectoris 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Pericarditis 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Sinus Tachycardia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Eye disorders
    Vision Blurred 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Dry Eye 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Eye Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Ocular Hyperaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Pupillary Reflex Impaired 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Gastrointestinal disorders
    Nausea 0/4 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 2/4 (50%) 1/6 (16.7%) 1/3 (33.3%)
    Diarrhoea 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 0/6 (0%) 2/3 (66.7%)
    Constipation 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Vomiting 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Dry Mouth 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Abdominal Distension 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Abdominal Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Abdominal Pain Upper 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Ascites 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Dysphagia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Enteritis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Eructation 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Gastrooesophageal Reflux Disease 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Lip Ulceration 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Melaena 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Mouth Ulceration 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Oral Mucosa Haematoma 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Tongue Coated 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Abdominal Pain Lower 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Flatulence 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Oral Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Stomatitis 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    General disorders
    Fatigue 0/4 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 2/4 (50%) 3/6 (50%) 1/3 (33.3%)
    Pyrexia 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 1/4 (25%) 1/6 (16.7%) 1/3 (33.3%)
    Oedema Peripheral 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Mucosal Inflammation 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Asthenia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Catheter Site Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Chills 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Non-cardiac Chest Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Gait Disturbance 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Peripheral Swelling 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 2/3 (66.7%)
    Immune system disorders
    Graft versus Host Disease 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Infections and infestations
    Pneumonia 0/4 (0%) 1/3 (33.3%) 1 0/3 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 0/3 (0%) 1 1/3 (33.3%) 1 1/4 (25%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1
    Anorectal Infection 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Device Related Infection 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Diverticulitis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Epiglottitis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Otitis Externa 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Pharyngitis 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Sinusitis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Injury, poisoning and procedural complications
    Contusion 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 1/3 (33.3%)
    Fall 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Head Injury 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Laceration 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Investigations
    Gamma-glutamyltransferase Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 4/6 (66.7%) 2/3 (66.7%)
    Aspartate Aminotransferase Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 2/6 (33.3%) 2/3 (66.7%)
    Alanine Aminotransferase Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 2/3 (66.7%)
    Neutrophil Count Decreased 0/4 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Blood Alkaline Phosphatase Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 2/3 (66.7%)
    Electrocardiogram QT Prolonged 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Activated Partial Thromboplastin Time Prolonged 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Blood Creatinine Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Ejection Fraction Decreased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Enterococcus Test Positive 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    International Normalised Ratio Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Liver Function Test Abnormal 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Platelet Count Decreased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Troponin I Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Weight Decreased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    White Blood Cell Count Decreased 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    White Blood Cell Count Increased 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Metabolism and nutrition disorders
    Decreased Appetite 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/4 (25%) 2/6 (33.3%) 2/3 (66.7%)
    Hypocalcaemia 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 1/6 (16.7%) 2/3 (66.7%)
    Hyperglycaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 2/3 (66.7%)
    Hyperkalaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 2/6 (33.3%) 1/3 (33.3%)
    Hypoalbuminaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 2/3 (66.7%)
    Hypophosphataemia 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Fluid Overload 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Hypokalaemia 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Hypomagnesaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Hyponatraemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Hypermagnesaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Hypertriglyceridaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Hyperphosphataemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Hyperuricaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Vitamin D Deficiency 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Back Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Muscular Weakness 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Flank Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Hypercreatinaemia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Myalgia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Myositis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Neck Pain 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Pain in Extremity 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Synovial Cyst 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Nervous system disorders
    Dizziness 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Paraesthesia 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Headache 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 2/6 (33.3%) 0/3 (0%)
    Autonomic Nervous System Imbalance 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Cognitive Disorder 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Dizziness Postural 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Dysgeusia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Presyncope 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Sinus Headache 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Psychiatric disorders
    Anxiety 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Insomnia 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Depression 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Mental Status Changes 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Confusional State 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Hallucination 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Irritability 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Renal and urinary disorders
    Proteinuria 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Haematuria 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Acute Kidney Injury 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Chronic Kidney Disease 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Reproductive system and breast disorders
    Balanoposthitis 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Cough 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Epistaxis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Oropharyngeal Pain 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Pleural Effusion 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 2/3 (66.7%)
    Atelectasis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Hypoxia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Nasal Congestion 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/4 (25%) 0/6 (0%) 0/3 (0%)
    Pneumonitis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Productive Cough 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Rhinitis Allergic 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Rhinorrhoea 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Sinus Congestion 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Wheezing 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Skin and subcutaneous tissue disorders
    Rash Maculo-papular 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Dry Skin 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Rash 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Pruritus 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Urticaria 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 1/3 (33.3%)
    Alopecia 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Blister 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Cold Sweat 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Decubitus Ulcer 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Dermal Cyst 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Ecchymosis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Erythema 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Hypersensitivity Vasculitis 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Petechiae 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Rash Pruritic 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Skin Discolouration 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Skin Exfoliation 0/4 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Skin Lesion 0/4 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Skin Mass 1/4 (25%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 0/3 (0%)
    Capillary Leak Syndrome 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 0/6 (0%) 1/3 (33.3%)
    Lymphoedema 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/4 (0%) 1/6 (16.7%) 0/3 (0%)
    Vascular disorders
    Hypertension 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/4 (25%) 1/6 (16.7%) 1/3 (33.3%)

    Limitations/Caveats

    Only a small number of participants were analyzed as the study was early terminated due to slow enrollment.

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title ADC Therapeutics
    Organization ADC Therapeutics
    Phone 954-903-7994
    Email clinical.trials@adctherapeutics.com
    Responsible Party:
    ADC Therapeutics S.A.
    ClinicalTrials.gov Identifier:
    NCT02588092
    Other Study ID Numbers:
    • ADCT-301-002
    First Posted:
    Oct 27, 2015
    Last Update Posted:
    Feb 26, 2020
    Last Verified:
    Feb 1, 2020