Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)

• Sponsor: ADC Therapeutics S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02669017
• Collaborator: (none)
• Enrollment: 183
• Locations: 11
• Arms: 2
• Duration (Months): 35.7
• Patients Per Site: 16.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia; Primary Mediastinal B-cell Lymphoma	Drug: ADCT-402	Phase 1

Detailed Description

Study ADCT-402-101 is the first clinical study with ADCT-402 in participants with B-cell Non Hodgkin Lymphoma (NHL).

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated via a valine-alanine cleavable, maleimide linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin.

The study will be conducted in 2 parts. In Part 1 (dose escalation) participants will receive infusions of ADCT-402, at escalating doses. Part 1 will continue until the maximum tolerated dose is determined. In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.

For each participant, the study will include a screening period (up to 28 days), a treatment period (until withdrawal), 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 duration of the entire study (Parts 1 and 2) could be approximately 3 years from first participant treated to last participant completed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 183 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Dose-escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Feb 21, 2019
• Actual Study Completion Date: Feb 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: ADCT-402 dose escalation In Part 1 (dose escalation) participants will receive intravenous (IV) infusions of ADCT-402 at escalating doses, according to a 3+3 study design. Doses will be escalated from 15 µg/kg to 200 µg/kg on Day 1 of each cycle, with cycle lengths of 3 or 6 weeks.	Drug: ADCT-402; intravenous infusion; Other Names: Loncastuximab tesirine Zynlonta
Experimental: Part 2: ADCT-402 dose expansion In Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee. Participants will receive intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).	Drug: ADCT-402; intravenous infusion; Other Names: Loncastuximab tesirine Zynlonta

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)]

   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: CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection. CTCAE Grade 4 neutropenia lasting >7 days. CTCAE Grade 4 thrombocytopenia. CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion. CTCAE Grade 4 anemia. A non-hematologic DLT is defined as: CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage. CTCAE 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 2 or higher skin ulceration.

2. Recommended Dose of ADCT-402 for Part 2 [Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)]

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

3. Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) [Day 1 to End of Study (a maximum of 18 months)]

   An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any 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 at Least One Treatment Emergent Serious Adverse Event (SAE) [Day 1 to End of Study (a maximum of 18 months)]

   An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any 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. 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.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Baseline to End of Study (a maximum of 18 months)]

   ORR was defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with ADCT-402, before the start of subsequent anticancer therapy or procedure. Tumor response was assessed using the 2014 Lugano Classification for response. CR is defined as achieving either of the following: Complete metabolic response. Complete radiologic response (target node regress to <1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR is defined as achieving either of the following: Partial metabolic response (findings indicate residual disease). Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by >50% in length and no new lesions).

2. Duration of Response (DoR) [Baseline to End of Study (a maximum of 18 months)]

   DoR is defined among responders (complete response [CR] and 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. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: Target node progression. An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%. New or clear progression of nonmeasured lesions. Regrowth of previously resolved lesions or new nodes >1.5 cm in length. New or recurrent bone marrow involvement. DoR is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

3. Overall Survival (OS) [Baseline to End of Study (a maximum of 18 months)]

   OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. OS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

4. Progression-free Survival (PFS) [Baseline to End of Study (a maximum of 18 months)]

   PFS is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: Target node progression. An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%. New or clear progression of nonmeasured lesions. Regrowth of previously resolved lesions or new nodes >1.5 cm in length. New or recurrent bone marrow involvement. PFS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

5. Maximum Observed Serum Concentration (Cmax) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

   Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

6. Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

   Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

7. Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

   AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

8. Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

   AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

9. Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

   AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

10. Terminal Half-life (Thalf) of ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

    Thalf of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

11. Apparent Clearance (CL) at Steady State for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

    CL of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

12. Volume of Distribution at Steady State (Vss) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

    Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

13. Accumulation Index (AI) for ADCT-402 [Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)]

    AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). 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 (Q3W schedule: 3 week cycle length; Q6W schedule: 6 week cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.

14. Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 [Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)]

    Blood serum samples were collected and analysed to determine the presence or absence of ADA. ADA is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female participants, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available.

• Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification system).

• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.

• Measurable disease, as defined by the 2014 Lugano Classification.

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

• Absolute neutrophil count (ANC) ≥1000/μL.

• Platelet count of ≥75000/μL.

• Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.

• Serum/plasma creatinine ≤1.5 mg/dL.

• Serum/plasma alkaline phosphatase, 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 ULN.

• Negative blood or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to Day 1 for women of childbearing potential.

• Males, and female participants who are biologically capable of having children, must agree to use a medically acceptable method of birth control.

Exclusion Criteria:

• Participants who have any option for other treatment for B-cell NHL at the current state of disease.

• Active graft-versus-host disease.

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

• Known history of immunogenicity or hypersensitivity to a CD19 antibody.

• Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.

• Known history of positive serum human ADA.

• Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease.

• Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV).

• History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.

• Pregnant or breastfeeding women.

• Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or 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 less than 14 days prior to start of study treatment on Cycle 1, Day 1, except if approved by Sponsor.

• Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days) prior to Day 1.

• Major surgery, chemotherapy, systemic therapy (excluding steroids hydroxyurea steroids, and any targeted small molecules or biologics), or radiotherapy, 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 Common Terminology Criteria for Adverse Events [CTCAE] Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.

• Congenital long QT syndrome or a corrected QTc interval ≥450 ms at the Screening visit.

• Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy determined not be exclusionary.

• Any other significant medical illness, abnormality, or condition that would make the participant inappropriate for study participation or put the participant at risk.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Columbia University Medical Center Herbert Irving Pavilion	New York	New York	United States	10032
6	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
7	Greenville Health System, Institute for Translational Oncology Research, Clinical Research Unit	Greenville	South Carolina	United States	29605
8	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
9	U.O Oncologia e Ematologia - Istituto Clinico Humanitas	Milano		Italy
10	University College London Hospitals	London		United Kingdom	NW1 2BU
11	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

• ADC Therapeutics S.A.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 16, 2017
• Statistical Analysis Plan - Jun 10, 2019

More Information

Publications

None provided.

• Responsible Party: ADC Therapeutics S.A.
• ClinicalTrials.gov Identifier: NCT02669017
• Other Study ID Numbers: ADCT-402-101; 2016-000952-92
• First Posted: Jan 29, 2016
• Last Update Posted: May 19, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by ADC Therapeutics S.A.: Loncastuximab tesirine
• Additional relevant MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Loncastuximab tesirine

Study Results

Participant Flow

Pre-assignment Detail	Participants were screened at 11 sites in 3 countries.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 2: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Period Title: Overall Study
STARTED	4	4	4	5	16	26	19	69	36
COMPLETED	3	2	2	1	4	7	8	7	11
NOT COMPLETED	1	2	2	4	12	19	11	62	25

Baseline Characteristics

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 2: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W	Total
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).	Total of all reporting groups
Overall Participants	4	4	4	5	16	26	19	69	36	183
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%
Between 18 and 65 years	1 25%	1 25%	3 75%	2 40%	3 18.8%	14 53.8%	13 68.4%	43 62.3%	19 52.8%	99 54.1%
>=65 years	3 75%	3 75%	1 25%	3 60%	13 81.3%	12 46.2%	6 31.6%	26 37.7%	17 47.2%	84 45.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.5 (8.39)	68.3 (11.53)	51.3 (18.82)	68.2 (12.38)	71.0 (10.20)	63.7 (13.37)	58.5 (13.96)	58.7 (15.82)	61.7 (12.82)	61.7 (14.49)
Sex: Female, Male (Count of Participants)
Female	2 50%	2 50%	2 50%	3 60%	3 18.8%	7 26.9%	6 31.6%	34 49.3%	10 27.8%	69 37.7%
Male	2 50%	2 50%	2 50%	2 40%	13 81.3%	19 73.1%	13 68.4%	35 50.7%	26 72.2%	114 62.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.8%	1 5.3%	3 4.3%	1 2.8%	6 3.3%
Not Hispanic or Latino	4 100%	4 100%	4 100%	5 100%	16 100%	25 96.2%	18 94.7%	65 94.2%	35 97.2%	176 96.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.4%	0 0%	1 0.5%
Race/Ethnicity, Customized (Count of Participants)
White	4 100%	4 100%	4 100%	4 80%	14 87.5%	19 73.1%	19 100%	61 88.4%	35 97.2%	164 89.6%
Black or African American	0 0%	0 0%	0 0%	1 20%	1 6.3%	4 15.4%	0 0%	5 7.2%	0 0%	11 6%
Asian	0 0%	0 0%	0 0%	0 0%	1 6.3%	2 7.7%	0 0%	0 0%	0 0%	3 1.6%
American Indian or Alaskan Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Other	0 0%	0 0%	0 0%	0 0%	0 0%	1 3.8%	0 0%	1 1.4%	1 2.8%	3 1.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 2.9%	0 0%	2 1.1%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	172.23 (18.438)	170.73 (12.545)	173.65 (11.544)	167.68 (10.275)	170.72 (8.977)	171.47 (9.790)	172.79 (10.584)	170.56 (11.908)	171.29 (12.193)	171.11 (11.221)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	73.65 (7.204)	78.73 (25.445)	79.95 (26.942)	86.38 (23.597)	86.89 (25.996)	78.66 (18.113)	88.67 (20.820)	77.87 (22.453)	88.71 (24.834)	82.23 (22.635)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	25.21 (3.971)	26.60 (5.466)	25.89 (5.428)	30.77 (8.931)	29.40 (6.882)	26.68 (5.458)	29.57 (5.575)	26.62 (6.648)	30.15 (7.235)	27.93 (6.587)
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0: Fully Active	2 50%	0 0%	2 50%	0 0%	7 43.8%	7 26.9%	4 21.1%	20 29%	12 33.3%	54 29.5%
1: Restricted in Physical Activity; Ambulatory	1 25%	3 75%	2 50%	4 80%	8 50%	19 73.1%	12 63.2%	36 52.2%	21 58.3%	106 57.9%
2: Ambulatory and Capable of All Self-care	1 25%	1 25%	0 0%	1 20%	1 6.3%	0 0%	2 10.5%	12 17.4%	3 8.3%	21 11.5%
3: Capable of Only Limited Self-care	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.3%	1 1.4%	0 0%	2 1.1%
4: Completely Disabled	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
5: Dead	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
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: CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection. CTCAE Grade 4 neutropenia lasting >7 days. CTCAE Grade 4 thrombocytopenia. CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion. CTCAE Grade 4 anemia. A non-hematologic DLT is defined as: CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage. CTCAE 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 2 or higher skin ulceration.
Time Frame	Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Outcome Measure Data

Analysis Population Description

All participants in Part 1 who completed at least one cycle of treatment.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Measure Participants	4	4	3	5	16	16	25
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	1 6.3%	1 3.8%	2 10.5%

2. Primary Outcome

Title	Recommended Dose of ADCT-402 for Part 2
Description	The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Time Frame	Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Outcome Measure Data

Analysis Population Description

All participants in Part 1 who completed at least one cycle of treatment.

Arm/Group Title	Part 1: ADCT-402 Dose Escalation
Arm/Group Description	In Part 1 (dose escalation) participants received intravenous (IV) infusions of ADCT-402, at escalating doses according to a 3+3 study design. Doses assessed: Dose Level 1: 15 μg/kg on Day 1 of each 3 week cycle (Q3W) Dose Level 2: 30 μg/kg Day 1 Q3W Dose Level 3: 60 μg/kg Day 1 Q3W Dose Level 4: 90 μg/kg Day 1 Q3W Dose Level 5: 120 μg/kg Day 1 Q3W Dose Level 6: 150 μg/kg Day 1 Q3W Dose Level 7: 200 μg/kg Day 1 Q3W and on Day 1 of each 6 week cycle (Q6W).
Measure Participants	73
Recommended Part 2 Dose 1	120
Recommended Part 2 Dose 2	150

3. Primary Outcome

Title	Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any 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 End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 2: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Measure Participants	4	4	4	5	16	26	19	69	36
Count of Participants [Participants]	4 100%	3 75%	4 100%	5 100%	16 100%	26 100%	19 100%	68 98.6%	36 100%

4. Primary Outcome

Title	Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any 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. 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.
Time Frame	Day 1 to End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 2: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Measure Participants	4	4	4	5	16	26	19	69	36
Count of Participants [Participants]	1 25%	1 25%	0 0%	4 80%	4 25%	14 53.8%	6 31.6%	40 58%	15 41.7%

5. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) at the time each participant discontinued treatment with ADCT-402, before the start of subsequent anticancer therapy or procedure. Tumor response was assessed using the 2014 Lugano Classification for response. CR is defined as achieving either of the following: Complete metabolic response. Complete radiologic response (target node regress to <1.5 cm, no nonmeasured lesions, no organ enlargement, no new lesions and normal bone marrow morphology). PR is defined as achieving either of the following: Partial metabolic response (findings indicate residual disease). Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of nonmeasured lesions, spleen regressed by >50% in length and no new lesions).
Time Frame	Baseline to End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Part 1: 120 μg/kg Q3W	Part 2: 120 μg/kg Q3W	Part 1: 150 μg/kg Q3W	Part 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
Measure Participants	4	4	4	5	16	26	19	68	34
Count of Participants [Participants]	1 25%	1 25%	1 25%	2 40%	9 56.3%	11 42.3%	12 63.2%	25 36.2%	20 55.6%

6. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR is defined among responders (complete response [CR] and 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. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: Target node progression. An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%. New or clear progression of nonmeasured lesions. Regrowth of previously resolved lesions or new nodes >1.5 cm in length. New or recurrent bone marrow involvement. DoR is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Time Frame	Baseline to End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment. Results are pooled for all arms as specified in the protocol.

Arm/Group Title	Parts 1 and 2: ADCT-402
Arm/Group Description	In Part 1 (dose escalation) participants received intravenous (IV) infusions of ADCT-402, at escalating doses according to a 3+3 study design. Doses assessed: Dose Level 1: 15 μg/kg on Day 1 of each 3 week cycle (Q3W) Dose Level 2: 30 μg/kg Day 1 Q3W Dose Level 3: 60 μg/kg Day 1 Q3W Dose Level 4: 90 μg/kg Day 1 Q3W Dose Level 5: 120 μg/kg Day 1 Q3W Dose Level 6: 150 μg/kg Day 1 Q3W Dose Level 7: 200 μg/kg Day 1 Q3W and on Day 1 of each 6 week cycle (Q6W). In Part 2 (expansion), participants received intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).
Measure Participants	180
Median (95% Confidence Interval) [months]	5.36

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. OS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Time Frame	Baseline to End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment. Results are pooled for all arms as specified in the protocol.

Arm/Group Title	Parts 1 and 2: ADCT-402
Arm/Group Description	In Part 1 (dose escalation) participants received intravenous (IV) infusions of ADCT-402, at escalating doses according to a 3+3 study design. Doses assessed: Dose Level 1: 15 μg/kg on Day 1 of each 3 week cycle (Q3W) Dose Level 2: 30 μg/kg Day 1 Q3W Dose Level 3: 60 μg/kg Day 1 Q3W Dose Level 4: 90 μg/kg Day 1 Q3W Dose Level 5: 120 μg/kg Day 1 Q3W Dose Level 6: 150 μg/kg Day 1 Q3W Dose Level 7: 200 μg/kg Day 1 Q3W and on Day 1 of each 6 week cycle (Q6W). In Part 2 (expansion), participants received intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).
Measure Participants	180
Median (95% Confidence Interval) [months]	8.25

8. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined among the efficacy population as the time from first dose of study drug until either disease progression or death due to any cause. Tumor response was assessed using the 2014 Lugano Classification for response. Disease progression is defined as progressive metabolic disease or one of the follow: Target node progression. An individual extranodal lesion must be abnormal with length >1.5cm and/or increase of length >50%. New or clear progression of nonmeasured lesions. Regrowth of previously resolved lesions or new nodes >1.5 cm in length. New or recurrent bone marrow involvement. PFS is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Time Frame	Baseline to End of Study (a maximum of 18 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment with a valid baseline disease assessment and at least one valid post-baseline disease assessment. Results are pooled for all arms as specified in the protocol.

Arm/Group Title	Parts 1 and 2: ADCT-402
Arm/Group Description	In Part 1 (dose escalation) participants received intravenous (IV) infusions of ADCT-402, at escalating doses according to a 3+3 study design. Doses assessed: Dose Level 1: 15 μg/kg on Day 1 of each 3 week cycle (Q3W) Dose Level 2: 30 μg/kg Day 1 Q3W Dose Level 3: 60 μg/kg Day 1 Q3W Dose Level 4: 90 μg/kg Day 1 Q3W Dose Level 5: 120 μg/kg Day 1 Q3W Dose Level 6: 150 μg/kg Day 1 Q3W Dose Level 7: 200 μg/kg Day 1 Q3W and on Day 1 of each 6 week cycle (Q6W). In Part 2 (expansion), participants received intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).
Measure Participants	180
Median (95% Confidence Interval) [months]	3.09

9. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) for ADCT-402
Description	Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	4	5	42	88	14	22
PBD conjugated Ab: Cycle 1	260 (85.5)	404 (161)	721 (481)	1088 (748)	2374 (1040)	3416 (3093)	3619 (688)	3798 (1332)
PBD conjugated Ab: Cycle 2	398 (284)	1971 (2566)	864 (686)	1416 (799)	2573 (655)	3776 (2738)	4293 (1021)	3178 (1733)
total Ab: Cycle 1	298 (83.7)	542 (192)	856 (475)	1560 (1102)	2829 (1257)	4383 (4460)	4185 (1308)	4543 (1805)
total Ab: Cycle 2	447 (283)	2906 (4034)	1275 (1025)	2422 (983)	3142 (888)	4798 (3334)	5059 (1027)	3834 (1913)
SG3199: Cycle 1	0.102 (NA)	0.0372 (0.0208)	0.0570 (0.0454)	0.0479 (0.0381)	0.0468 (0.0333)
SG3199: Cycle 2	0.0704 (0.0152)	0.0403 (0.0116)	0.0485 (0.0449)	0.0293 (0.00329)	0.0516 (0.0325)

10. Secondary Outcome

Title	Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402
Description	Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	4	5	42	88	14	22
PBD conjugated Ab: Cycle 1	0.0837	0.0833	0.0819	0.0500	0.0833	0.0840	0.0858	0.0840
PBD conjugated Ab: Cycle 2	0.122	0.0618	0.0417	0.0833	0.0830	0.0642	0.0854	0.0826
total Ab: Cycle 1	0.0844	0.0833	0.0833	0.0500	0.0833	0.0837	0.0840	0.0837
total Ab: Cycle 2	0.0649	0.0618	0.0417	0.0833	0.0632	0.0639	0.132	0.0858
SG3199: Cycle 1	0.0833	0.0854	0.0844	0.128	0.165
SG3199: Cycle 2	1.05	0.120	0.0632	0.165	0.162

11. Secondary Outcome

Title	Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402
Description	AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	4	5	42	88	14	22
PBD conjugated Ab: Cycle 1	1063 (1340)	2390 (826)	3875 (3228)	6587 (6842)	13544 (7503)	14258 (8248)	30571 (12425)	30386 (16960)
PBD conjugated Ab: Cycle 2	1933 (2289)	2955 (1132)	5573 (4827)	10369 (11656)	18707 (10505)	23109 (15370)	48183 (20288)	39609 (24852)
total Ab: Cycle 1	1185 (1540)	3194 (1136)	5032 (4334)	8869 (9108)	15980 (7649)	16973 (9745)	33834 (14888)	36099 (20829)
total Ab: Cycle 2	1924 (2576)	3986 (1725)	7958 (6882)	14025 (15704)	23428 (13513)	28657 (19457)	57450 (26899)	49892 (31012)
SG3199: Cycle 1	0.00213 (NA)	0.00462 (0.00671)	0.0222 (0.0423)	0.0174 (0.0303)	0.0436 (0.0959)
SG3199: Cycle 2	0.0242 (0.0234)	0.154 (0.286)	0.0108 (0.0248)	0.00425 (0.00461)	0.00332 (0.00215)

12. Secondary Outcome

Title	Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402
Description	AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	3	5	40	72	11	12
PBD conjugated Ab: Cycle 2	2285 (2928)	3458 (1426)	10575 (1121)	10171 (11244)	19890 (8968)	22859 (12080)	39362 (9800)	38466 (23514)
total Ab: Cycle 2	2636 (3387)	4662 (2096)	10211 (8827)	17141 (15029)	24247 (10902)	28041 (15312)	46469 (12675)	48524 (28858)

13. Secondary Outcome

Title	Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402
Description	AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	3	2	2	2	15	47	4	13
PBD conjugated Ab: Cycle 1	432 (173)	2001 (663)	5333 (4002)	5622 (7170)	10232 (6220)	11498 (8175)	29174 (25838)	32629 (19488)
total Ab: Cycle 1	869 (NA)	16409 (NA)	13292 (8495)	12692 (8968)	38991 (53597)	43952 (24032)
SG3199: Cycle 1	0.154 (NA)

14. Secondary Outcome

Title	Terminal Half-life (Thalf) of ADCT-402
Description	Thalf of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	2	4	38	69	11	13
PBD conjugated Ab: Cycle 1	1.15	6.84	6.30	3.97	6.33	6.43	7.96	10.4
PBD conjugated Ab: Cycle 2	3.98	10.1	16.3	11.4	12.5	11.6	16.3	15.5
total Ab: Cycle 1	2.75	8.82	7.00	6.58	9.39	12.7
total Ab: Cycle 2	3.71	9.58	16.5	13.4	14.9	14.3	14.7	18.4

15. Secondary Outcome

Title	Apparent Clearance (CL) at Steady State for ADCT-402
Description	CL of Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	3	5	40	72	11	13
PBD conjugated Ab: Cycle 1	2.49 (0.978)	1.08 (0.164)	0.696 (0.444)	7.13 (8.91)	2.09 (4.07)	3.84 (8.53)	3.11 (5.30)	12.6 (39.4)
PBD conjugated Ab: Cycle 2	1.78 (1.80)	0.646 (0.348)	0.415 (0.205)	19.6 (40.6)	17.8 (109)	0.986 (2.48)	0.407 (0.143)	0.349 (0.210)
total Ab: Cycle 1	1.28 (NA)	0.640 (NA)	2.47 (5.00)	3.87 (8.95)	7.12 (9.62)	2.02 (5.11)
total Ab: Cycle 2	1.76 (1.71)	0.577 (0.309)	38.1 (65.5)	1.42 (2.06)	0.581 (0.660)	1.05 (2.91)	0.417 (0.161)	0.323 (0.187)
SG3199: Cycle 1	627 (NA)

16. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) for ADCT-402
Description	Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	2	4	38	69	11	13
PBD conjugated Ab: Cycle 1	4.47 (0.759)	10.3 (4.83)	4.96 (0.318)	9.68 (2.68)	5.95 (1.86)	7.59 (6.18)	11.5 (11.1)	7.18 (2.52)
PBD conjugated Ab: Cycle 2	3.82 (1.25)	10.1 (8.57)	8.29 (0.540)	7.62 (1.09)	6.71 (3.13)	7.48 (4.29)	9.18 (3.43)	6.21 (1.70)
total Ab: Cycle 1	4.71 (NA)	7.84 (NA)	5.51 (1.29)	6.60 (3.16)	7.91 (0.0252)	7.20 (2.03)
total Ab: Cycle 2	3.83 (0.854)	9.62 (8.54)	7.30 (1.38)	8.52 (1.34)	8.11 (4.57)	8.21 (3.64)	9.46 (5.26)	6.86 (2.27)
SG3199: Cycle 1	335 (NA)

17. Secondary Outcome

Title	Accumulation Index (AI) for ADCT-402
Description	AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199). 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 (Q3W schedule: 3 week cycle length; Q6W schedule: 6 week cycle length). It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. Results for Part 1 and Part 2 have been pooled for the same dosage and schedule, as specified in the protocol.
Time Frame	Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)

Outcome Measure Data

Analysis Population Description

Only participants with evaluable pharmacokinetic (PK) results were included in the analysis. Where data is not presented, the PK profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.

Arm/Group Title	Part 1: 15 μg/kg Q3W	Part 1: 30 μg/kg Q3W	Part 1: 60 μg/kg Q3W	Part 1: 90 μg/kg Q3W	Parts 1 and 2: 120 μg/kg Q3W	Parts 1 and 2: 150 μg/kg Q3W	Part 1: 200 μg/kg Q3W	Part 1: 200 μg/kg Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).	Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). Parts 1 and 2 are pooled for PK analysis as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.	Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 6 week cycle (Q6W). Analysis was performed separately for Q3W and Q6W treatment cycles as specified in the protocol.
Measure Participants	4	4	2	4	38	69	11	12
PBD conjugated Ab: Cycle 2	1.12 (0.173)	1.37 (0.264)	1.70 (0.467)	1.42 (0.399)	1.47 (0.369)	1.46 (0.368)	1.76 (0.385)	1.23 (0.160)
total Ab: Cycle 2	1.15 (0.229)	1.35 (0.252)	1.71 (0.325)	1.80 (0.962)	1.62 (0.492)	1.63 (0.486)	1.78 (0.418)	1.36 (0.314)

18. Secondary Outcome

Title	Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402
Description	Blood serum samples were collected and analysed to determine the presence or absence of ADA. ADA is presented overall for all participants who received ADCT-402, as specified in protocol section 7.4.
Time Frame	Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)

Outcome Measure Data

Analysis Population Description

All participants who were tested for ADA.

Arm/Group Title	Parts 1 and 2: ADCT-402
Arm/Group Description	In Part 1 (dose escalation) participants received intravenous (IV) infusions of ADCT-402, at escalating doses according to a 3+3 study design. Doses assessed: Dose Level 1: 15 μg/kg on Day 1 of each 3 week cycle (Q3W) Dose Level 2: 30 μg/kg Day 1 Q3W Dose Level 3: 60 μg/kg Day 1 Q3W Dose Level 4: 90 μg/kg Day 1 Q3W Dose Level 5: 120 μg/kg Day 1 Q3W Dose Level 6: 150 μg/kg Day 1 Q3W Dose Level 7: 200 μg/kg Day 1 Q3W and on Day 1 of each 6 week cycle (Q6W). In Part 2 (expansion), participants received intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).
Measure Participants	183
Confirmed positive ADA pre-dose	5 125%
Confirmed positive ADA post-dose only	1 25%
Confirmed positive ADA at anytime	6 150%

Adverse Events

Time Frame	Day 1 to End of Study (a maximum of 18 months)
Arm/Group Title	Part 1: 15 μg/kg Q3W		Part 1: 30 μg/kg Q3W		Part 1: 60 μg/kg Q3W		Part 1: 90 μg/kg Q3W		Part 1: 120 μg/kg Q3W		Part 2: 120 μg/kg Q3W		Part 1: 150 μg/kg Q3W		Part 2: 150 μg/kg Q3W		Part 1: 200 μg/kg Q3W and Q6W
Arm/Group Description	Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W).		Participants received an intravenous (IV) infusion of ADCT-402 (200 μg/kg) on Day 1 of each 3 week cycle (Q3W). Following protocol amendment 5, treatment cycle length was increased to 6 weeks (Q6W).
All Cause Mortality
	Part 1: 15 μg/kg Q3W		Part 1: 30 μg/kg Q3W		Part 1: 60 μg/kg Q3W		Part 1: 90 μg/kg Q3W		Part 1: 120 μg/kg Q3W		Part 2: 120 μg/kg Q3W		Part 1: 150 μg/kg Q3W		Part 2: 150 μg/kg Q3W		Part 1: 200 μg/kg Q3W and Q6W
	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	1/4 (25%)		2/4 (50%)		2/4 (50%)		3/5 (60%)		8/16 (50%)		18/26 (69.2%)		10/19 (52.6%)		47/69 (68.1%)		20/36 (55.6%)
Serious Adverse Events
	Part 1: 15 μg/kg Q3W		Part 1: 30 μg/kg Q3W		Part 1: 60 μg/kg Q3W		Part 1: 90 μg/kg Q3W		Part 1: 120 μg/kg Q3W		Part 2: 120 μg/kg Q3W		Part 1: 150 μg/kg Q3W		Part 2: 150 μg/kg Q3W		Part 1: 200 μg/kg Q3W and Q6W
	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	1/4 (25%)		1/4 (25%)		0/4 (0%)		4/5 (80%)		4/16 (25%)		4/26 (15.4%)		6/19 (31.6%)		40/69 (58%)		15/36 (41.7%)
Blood and lymphatic system disorders
Febrile neutropenia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/16 (6.3%)		1/26 (3.8%)		1/19 (5.3%)		5/69 (7.2%)		1/36 (2.8%)
Anaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Neutropenia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Cardiac disorders
Pericardial effusion	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Cardiac arrest	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Supraventricular tachycardia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Endocrine disorders
Hypothyroidism	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Gastrointestinal disorders
Abdominal pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Gastrointestinal haemorrhage	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Nausea	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Small intestinal obstruction	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Abdominal compartment syndrome	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Abdominal distension	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Anal fissure	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Constipation	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Diarrhoea	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Intestinal obstruction	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Intestinal perforation	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Lower gastrointestinal haemorrhage	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Melaena	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Rectal haemorrhage	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
General disorders
Disease progression	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		8/69 (11.6%)		0/36 (0%)
Pyrexia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		4/26 (15.4%)		1/19 (5.3%)		2/69 (2.9%)		0/36 (0%)
General physical health deterioration	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		2/36 (5.6%)
Fatigue	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Generalised oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		1/69 (1.4%)		0/36 (0%)
Gait disturbance	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Injection site extravasation	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Non-cardiac chest pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Oedema peripheral	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Hepatobiliary disorders
Hepatic failure	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Infections and infestations
Sepsis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		4/69 (5.8%)		0/36 (0%)
Lung infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Cellulitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Pneumonia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Clostridium difficile colitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Clostridium difficile infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Cytomegalovirus infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Enterocolitis infectious	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Influenza	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Lower respiratory tract infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Oesophageal candidiasis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Oropharyngeal candidiasis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Parainfluenzae virus infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Pneumonia haemophilus	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Pneumonia influenzal	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Pneumonia staphylococcal	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Progressive multifocal leukoencephalopathy	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Rhinovirus infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Septic shock	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Staphylococcal sepsis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Upper respiratory tract infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Injury, poisoning and procedural complications
Procedural pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Subdural haematoma	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Wound	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Investigations
Alanine aminotransferase increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Aspartate aminotransferase increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Gamma-glutamyltransferase increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Platelet count decreased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Metabolism and nutrition disorders
Fluid overload	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Failure to thrive	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Hypokalaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Hyponatraemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		1/69 (1.4%)		0/36 (0%)
Arthralgia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Neck mass	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large B-cell lymphoma	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		2/26 (7.7%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Lymphoma	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Burkitt's lymphoma	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Mantle cell lymphoma	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Nervous system disorders
Aphasia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Depressed level of consciousness	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Headache	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Paraesthesia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Syncope	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Psychiatric disorders
Confusional state	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Disorientation	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Mental status changes	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Renal and urinary disorders
Acute kidney injury	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		1/69 (1.4%)		1/36 (2.8%)
Haematuria	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Urinary retention	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Reproductive system and breast disorders
Oedema genital	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Perineal pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Scrotal pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		2/69 (2.9%)		3/36 (8.3%)
Dyspnoea	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		1/19 (5.3%)		3/69 (4.3%)		1/36 (2.8%)
Pneumonitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Pulmonary embolism	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Hypoxia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Pneumomediastinum	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Pneumonia aspiration	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Pulmonary oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Vascular disorders
Embolism	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Lymphoedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: 15 μg/kg Q3W		Part 1: 30 μg/kg Q3W		Part 1: 60 μg/kg Q3W		Part 1: 90 μg/kg Q3W		Part 1: 120 μg/kg Q3W		Part 2: 120 μg/kg Q3W		Part 1: 150 μg/kg Q3W		Part 2: 150 μg/kg Q3W		Part 1: 200 μg/kg Q3W and Q6W
	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%)		3/4 (75%)		4/4 (100%)		5/5 (100%)		16/16 (100%)		25/26 (96.2%)		19/19 (100%)		65/69 (94.2%)		36/36 (100%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		1/16 (6.3%)		9/26 (34.6%)		7/19 (36.8%)		25/69 (36.2%)		14/36 (38.9%)
Neutropenia	0/4 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		3/16 (18.8%)		4/26 (15.4%)		3/19 (15.8%)		17/69 (24.6%)		10/36 (27.8%)
Thrombocytopenia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		3/16 (18.8%)		6/26 (23.1%)		3/19 (15.8%)		13/69 (18.8%)		9/36 (25%)
Lymphopenia	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Leukopenia	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Cardiac disorders
Pericardial effusion	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		3/26 (11.5%)		0/19 (0%)		3/69 (4.3%)		3/36 (8.3%)
Atrial fibrillation	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		1/26 (3.8%)		2/19 (10.5%)		2/69 (2.9%)		1/36 (2.8%)
Eye disorders
Periorbital oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		1/26 (3.8%)		1/19 (5.3%)		5/69 (7.2%)		0/36 (0%)
Dry eye	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		3/69 (4.3%)		2/36 (5.6%)
Visual impairment	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Gastrointestinal disorders
Nausea	1/4 (25%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		4/16 (25%)		8/26 (30.8%)		5/19 (26.3%)		22/69 (31.9%)		16/36 (44.4%)
Constipation	0/4 (0%)		0/4 (0%)		0/4 (0%)		2/5 (40%)		2/16 (12.5%)		9/26 (34.6%)		2/19 (10.5%)		18/69 (26.1%)		6/36 (16.7%)
Vomiting	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		2/16 (12.5%)		5/26 (19.2%)		2/19 (10.5%)		15/69 (21.7%)		7/36 (19.4%)
Diarrhoea	1/4 (25%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		3/16 (18.8%)		2/26 (7.7%)		3/19 (15.8%)		13/69 (18.8%)		5/36 (13.9%)
Abdominal pain	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		6/26 (23.1%)		4/19 (21.1%)		7/69 (10.1%)		7/36 (19.4%)
Abdominal distension	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		2/26 (7.7%)		2/19 (10.5%)		4/69 (5.8%)		2/36 (5.6%)
Abdominal pain upper	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		5/69 (7.2%)		2/36 (5.6%)
Dyspepsia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		2/69 (2.9%)		3/36 (8.3%)
Dry mouth	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		4/69 (5.8%)		2/36 (5.6%)
Anal incontinence	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Salivary hypersecretion	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
General disorders
Fatigue	1/4 (25%)		1/4 (25%)		2/4 (50%)		3/5 (60%)		11/16 (68.8%)		11/26 (42.3%)		8/19 (42.1%)		24/69 (34.8%)		16/36 (44.4%)
Oedema peripheral	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		8/16 (50%)		4/26 (15.4%)		9/19 (47.4%)		22/69 (31.9%)		14/36 (38.9%)
Pyrexia	1/4 (25%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		6/26 (23.1%)		2/19 (10.5%)		8/69 (11.6%)		11/36 (30.6%)
Asthenia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		2/19 (10.5%)		2/69 (2.9%)		4/36 (11.1%)
Face oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		1/26 (3.8%)		0/19 (0%)		3/69 (4.3%)		4/36 (11.1%)
Non-cardiac chest pain	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		2/16 (12.5%)		0/26 (0%)		1/19 (5.3%)		2/69 (2.9%)		4/36 (11.1%)
Chills	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		2/69 (2.9%)		3/36 (8.3%)
Localised oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		1/26 (3.8%)		0/19 (0%)		4/69 (5.8%)		0/36 (0%)
Pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		5/69 (7.2%)		1/36 (2.8%)
Malaise	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		3/36 (8.3%)
Axillary pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Immune system disorders
Food allergy	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Infections and infestations
Urinary tract infection	1/4 (25%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		1/26 (3.8%)		1/19 (5.3%)		7/69 (10.1%)		0/36 (0%)
Cellulitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		3/19 (15.8%)		3/69 (4.3%)		0/36 (0%)
Rhinitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		5/69 (7.2%)		1/36 (2.8%)
Pneumonia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		2/69 (2.9%)		1/36 (2.8%)
Clostridium difficile infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Upper respiratory tract infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Oral candidiasis	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Respiratory tract infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		2/36 (5.6%)
Clostridium difficile colitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Influenza	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Sinusitis	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		2/36 (5.6%)
Corona virus infection	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Pyelonephritis acute	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Injury, poisoning and procedural complications
Fall	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		3/26 (11.5%)		4/19 (21.1%)		7/69 (10.1%)		0/36 (0%)
Contusion	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		3/19 (15.8%)		2/69 (2.9%)		1/36 (2.8%)
Skin abrasion	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/16 (6.3%)		0/26 (0%)		1/19 (5.3%)		1/69 (1.4%)		1/36 (2.8%)
Investigations
Gamma-glutamyltransferase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		4/5 (80%)		4/16 (25%)		9/26 (34.6%)		3/19 (15.8%)		19/69 (27.5%)		17/36 (47.2%)
Blood alkaline phosphatase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		1/16 (6.3%)		5/26 (19.2%)		2/19 (10.5%)		16/69 (23.2%)		9/36 (25%)
Aspartate aminotransferase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		1/16 (6.3%)		4/26 (15.4%)		1/19 (5.3%)		14/69 (20.3%)		11/36 (30.6%)
Platelet count decreased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		7/26 (26.9%)		3/19 (15.8%)		11/69 (15.9%)		11/36 (30.6%)
Alanine aminotransferase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		1/16 (6.3%)		5/26 (19.2%)		3/19 (15.8%)		11/69 (15.9%)		9/36 (25%)
Neutrophil count decreased	1/4 (25%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		3/16 (18.8%)		3/26 (11.5%)		5/19 (26.3%)		8/69 (11.6%)		8/36 (22.2%)
White blood cell count decreased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		5/26 (19.2%)		2/19 (10.5%)		4/69 (5.8%)		9/36 (25%)
Lymphocyte count decreased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		4/26 (15.4%)		1/19 (5.3%)		6/69 (8.7%)		6/36 (16.7%)
Blood creatinine increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		3/26 (11.5%)		2/19 (10.5%)		2/69 (2.9%)		3/36 (8.3%)
Weight decreased	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/16 (12.5%)		1/26 (3.8%)		1/19 (5.3%)		2/69 (2.9%)		3/36 (8.3%)
Blood bilirubin increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		3/69 (4.3%)		3/36 (8.3%)
Amylase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
Blood cholesterol increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		3/26 (11.5%)		0/19 (0%)		0/69 (0%)		2/36 (5.6%)
Lipase increased	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		1/36 (2.8%)
International normalised ratio increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		2/36 (5.6%)
Blood bicarbonate increased	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/4 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		1/16 (6.3%)		6/26 (23.1%)		2/19 (10.5%)		11/69 (15.9%)		12/36 (33.3%)
Hypokalaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/16 (12.5%)		1/26 (3.8%)		3/19 (15.8%)		12/69 (17.4%)		4/36 (11.1%)
Hyperglycaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		3/26 (11.5%)		3/19 (15.8%)		7/69 (10.1%)		5/36 (13.9%)
Hyponatraemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		4/26 (15.4%)		1/19 (5.3%)		5/69 (7.2%)		2/36 (5.6%)
Hypomagnesaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		1/19 (5.3%)		8/69 (11.6%)		2/36 (5.6%)
Dehydration	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		2/69 (2.9%)		6/36 (16.7%)
Hypocalcaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		3/69 (4.3%)		3/36 (8.3%)
Hypertriglyceridaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		2/69 (2.9%)		4/36 (11.1%)
Hypoalbuminaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		4/69 (5.8%)		3/36 (8.3%)
Hypophosphataemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		2/26 (7.7%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Hypercalcaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Hyperuricaemia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Gout	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		3/16 (18.8%)		1/26 (3.8%)		1/19 (5.3%)		3/69 (4.3%)		9/36 (25%)
Back pain	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		4/26 (15.4%)		3/19 (15.8%)		5/69 (7.2%)		1/36 (2.8%)
Pain in extremity	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		2/26 (7.7%)		1/19 (5.3%)		7/69 (10.1%)		3/36 (8.3%)
Muscular weakness	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		2/19 (10.5%)		4/69 (5.8%)		2/36 (5.6%)
Arthralgia	1/4 (25%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/16 (12.5%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		4/36 (11.1%)
Musculoskeletal pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		0/26 (0%)		1/19 (5.3%)		4/69 (5.8%)		1/36 (2.8%)
Neck pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		2/19 (10.5%)		2/69 (2.9%)		2/36 (5.6%)
Bone pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Joint swelling	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		0/36 (0%)
Limb mass	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Muscle twitching	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Nervous system disorders
Dizziness	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		5/26 (19.2%)		4/19 (21.1%)		5/69 (7.2%)		4/36 (11.1%)
Headache	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		3/26 (11.5%)		2/19 (10.5%)		4/69 (5.8%)		5/36 (13.9%)
Dysgeusia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		1/26 (3.8%)		0/19 (0%)		2/69 (2.9%)		2/36 (5.6%)
Neuropathy peripheral	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		2/69 (2.9%)		1/36 (2.8%)
Peripheral sensory neuropathy	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/16 (6.3%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Psychiatric disorders
Insomnia	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		2/26 (7.7%)		1/19 (5.3%)		4/69 (5.8%)		4/36 (11.1%)
Anxiety	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		1/26 (3.8%)		0/19 (0%)		1/69 (1.4%)		3/36 (8.3%)
Renal and urinary disorders
Bladder spasm	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Urinary retention	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Reproductive system and breast disorders
Breast oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		4/16 (25%)		7/26 (26.9%)		4/19 (21.1%)		15/69 (21.7%)		7/36 (19.4%)
Pleural effusion	0/4 (0%)		0/4 (0%)		0/4 (0%)		2/5 (40%)		4/16 (25%)		4/26 (15.4%)		3/19 (15.8%)		15/69 (21.7%)		8/36 (22.2%)
Cough	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		3/16 (18.8%)		7/26 (26.9%)		2/19 (10.5%)		14/69 (20.3%)		8/36 (22.2%)
Nasal congestion	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/16 (6.3%)		2/26 (7.7%)		1/19 (5.3%)		2/69 (2.9%)		3/36 (8.3%)
Productive cough	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/16 (12.5%)		1/26 (3.8%)		1/19 (5.3%)		3/69 (4.3%)		1/36 (2.8%)
Oropharyngeal pain	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		2/26 (7.7%)		2/19 (10.5%)		1/69 (1.4%)		0/36 (0%)
Chronic obstructive pulmonary disease	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Organising pneumonia	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Pulmonary oedema	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Sinus congestion	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		3/16 (18.8%)		4/26 (15.4%)		8/19 (42.1%)		19/69 (27.5%)		9/36 (25%)
Erythema	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/16 (12.5%)		3/26 (11.5%)		2/19 (10.5%)		9/69 (13%)		4/36 (11.1%)
Pruritus	1/4 (25%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		2/16 (12.5%)		2/26 (7.7%)		2/19 (10.5%)		5/69 (7.2%)		7/36 (19.4%)
Rash maculo-papular	1/4 (25%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		3/16 (18.8%)		1/26 (3.8%)		2/19 (10.5%)		5/69 (7.2%)		5/36 (13.9%)
Skin hyperpigmentation	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		3/16 (18.8%)		0/26 (0%)		2/19 (10.5%)		3/69 (4.3%)		4/36 (11.1%)
Photosensitivity reaction	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		3/16 (18.8%)		1/26 (3.8%)		1/19 (5.3%)		2/69 (2.9%)		3/36 (8.3%)
Dry skin	1/4 (25%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		1/16 (6.3%)		2/26 (7.7%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Dermatitis bullous	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		2/19 (10.5%)		1/69 (1.4%)		4/36 (11.1%)
Rash pruritic	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		1/26 (3.8%)		2/19 (10.5%)		2/69 (2.9%)		3/36 (8.3%)
Night sweats	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		2/26 (7.7%)		1/19 (5.3%)		2/69 (2.9%)		1/36 (2.8%)
Skin ulcer	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		2/36 (5.6%)
Decubitus ulcer	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		1/36 (2.8%)
Pruritus generalised	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		1/26 (3.8%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Rash macular	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		1/19 (5.3%)		0/69 (0%)		0/36 (0%)
Skin lesion	0/4 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		1/69 (1.4%)		0/36 (0%)
Dermatitis acneiform	1/4 (25%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Drug eruption	0/4 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/16 (0%)		0/26 (0%)		0/19 (0%)		0/69 (0%)		0/36 (0%)
Vascular disorders
Hypertension	0/4 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		2/16 (12.5%)		3/26 (11.5%)		0/19 (0%)		4/69 (5.8%)		4/36 (11.1%)
Hypotension	2/4 (50%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/16 (6.3%)		3/26 (11.5%)		1/19 (5.3%)		3/69 (4.3%)		4/36 (11.1%)
Flushing	0/4 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/16 (0%)		3/26 (11.5%)		1/19 (5.3%)		3/69 (4.3%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI can publish after first multi-site publication, or if no multi-site publication is made within 18 months of study completion/termination. The only disclosure restriction on the PI is the sponsor can review results comms. prior to public release and can embargo comms. regarding trial results for a period that is more than 60 but less than or equal to 180 days from the time submitted to sponsor for review. The sponsor can't require changes to the communication and can't extend the embargo.