Bladder Cancer, Breast Cancer, GastroEsophageal Cancer, Non Small Cell Lung Cancer
Conditions
Brief summary
This study evaluated ADCT-502 in participants with Advanced Solid Tumors with HER2 Expression. Participants participated in a dose-escalation phase (Part 1) and were due to participate in the dose expansion phase (Part 2). In Part 2, patients were due to receive the dose level identified in Part 1, but the study was terminated prior to the beginning of Part 2.
Detailed description
Study ADCT-502-101 was the first clinical study with ADCT-502 in participants with Advanced Solid Tumors with HER2 Expression. ADCT-502 is an antibody drug conjugate (ADC) composed of an engineered version of the humanized monoclonal antibody trastuzumab, directed against the human HER2 receptor, conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. ADCT-502 specifically binds to HER2, and once internalized, releases the PBD dimer to allow cross-linking of DNA and eventually trigger cell death. The study had 2 parts. In Part 1 (dose escalation) participants received an infusion of ADCT-502, at escalating doses. Part 1 continued until the maximum tolerated dose or the recommended dose(s) and schedule(s) for expansion were determined. In Part 2 (expansion), participants were due to be assigned to the recommended dose level of ADCT-502 identified in Part 1 by the Dose Escalation Steering Committee, but the study was terminated prior to the beginning of Part 2. For each participant, the study included a screening period (up to 28 days), a treatment period, and a follow-up period to assess disease progression and survival for up to 12 weeks after the last dose of study drug. The total study duration was dependent on overall participant tolerability to the study drug and response to treatment as participants were able to continue treatment until disease progression or unacceptable toxicity.
Interventions
DRUGADCT-502
Intravenous Infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Male or female age 18 years or older * Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition. * Eastern Cooperative Oncology Group (ECOG) performance status: Part 1: 0-2, Part 2: 0-1 * Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block or unstained slides to demonstrate HER2 expression. * Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening with documented HER2 expression. * Part 2/Dose Expansion Only: Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥1.5× 109/L). * Platelet count ≥100,000 //mm3 (≥100 × 109/L). * Hemoglobin ≥ 9 g/L (≥5.6 mmol/L). * Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); or ≤ 5.0 × ULN if liver metastases are present. * Total bilirubin ≤ 1.5× ULN (or ≤ 3× ULN, with direct bilirubin ≤1.5 × ULN, in participants with known Gilbert syndrome). * Creatinine ≤ 1.5× ULN; or, if serum creatinine \> 1.5 × ULN, a measured creatinine clearance must be \>60mL/min/1.73m2 as calculated by the Cockcroft and Gault equation for participants to be eligible. * Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the last dose of ADCT-502. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception from the time of giving informed consent until at least 16 weeks after the participant receives his last dose of ADCT-502. Main
Exclusion criteria
* Known history of ≥ Grade 3 hypersensitivity to a therapeutic antibody. * Known history of positive serum human anti-drug antibody (ADA) to trastuzumab. * Major surgical procedure or significant traumatic injury, radiotherapy, chemotherapy, targeted therapy, hormone therapy, or other anticancer therapy. * Failure to recover to Grade 0 or Grade 1 from acute non-hematologic toxicity due to previous therapy, prior to screening (with the exception of alopecia). * Central Nervous System (CNS) disease only. * Symptomatic CNS metastases or evidence of leptomeningeal disease. * Active cardiovascular disease or significant history thereof. * Other active disease including but not limited to ulceration of the upper gastrointestinal tract, autoimmune disease, HIV infection, active Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. * Breastfeeding or pregnant. * Other concurrent severe and/or uncontrolled medical conditions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities | Day 1 to 3 Weeks (one cycle) | — |
| Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | Day 1 to 3 Weeks (one cycle) | The Common Terminology Criteria For Adverse Events (CTCAE) Version 4 will be used. |
| Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. |
| Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | — |
| Number of Participants With Clinically Significant Clinical Laboratory Tests | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Physical Examination Results | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | Clinical significance was determined by the investigator. |
| Number of Participants Who Experience a Clinically Significant Change in Eastern Cooperative Oncology Group (ECOG) Performance Status | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | Performance status was assessed using the ECOG performance status grades. These range between Grade 0 (fully active) and Grade 5 (dead). Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Significant Vital Signs | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | Vital sign measurements include arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator. |
| Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | Day 1 to end of trial, a maximum of 168 days (+ 30 days) | Standard 12-lead ECG's will be used. Clinical significance was determined by the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) for ADCT-502 (Total Antibody) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Maximum Observed Plasma Concentration (Cmax) for Drug To-antibody Ratio [DAR] ≥0 | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Maximum Observed Plasma Concentration (Cmax) for PBD-conjugated Antibody (DAR ≥1) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Maximum Observed Plasma Concentration (Cmax) for Free Warhead SG3199 | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Overall Response Rate (ORR) | Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks | 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 discontinues ADCT-502. Analysis will be determined by the investigator per Response Evaluation In Solid Criteria (RECIST) version 1.1 criteria: partial response is when there is a decrease in sum of target disease ≥ 30%, and complete response is when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each. |
| Time to Reach the Maximum Plasma Concentration (Tmax) for Drug To-antibody Ratio [DAR] ≥0) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Time to Reach the Maximum Plasma Concentration (Tmax) for PBD-conjugated Antibody (DAR ≥1) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Time to Reach the Maximum Plasma Concentration (Tmax) for Free Warhead SG3199 | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Anti-drug Antibody (ADA) Titers to ADCT-502 | Blood sample collection before start of infusion in Cycles 1 and 2, and on Day 1 starting with Cycle 3 until disease progression, 30 days and 12 weeks after last dose | — |
| Time to Reach the Maximum Plasma Concentration (Tmax) for ADCT-502 (Total Antibody) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Disease Control Rate (DCR) | Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks | DCR was defined as the number of participants with a best overall response of Complete Response (CR) or Partial Response (PR), or Stable Disease (SD). Analysis will be determined by the investigator per Response Evaluation In Solid Criteria (RECIST) version 1.1 criteria: stable disease is when the change is \> -30% and ≤ 20%, partial response is when there is a decrease in sum of target disease ≥ 30%, and complete response is when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each. |
| Duration of Response (DOR) | Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks | DOR was defined among responders (CR or 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. |
| Progression-Free Survival (PFS) | Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks | PFS was defined among the efficacy population as the time from first dose of study drug until the first date of either disease progression or death due to any cause. |
| Overall Survival (OS) | Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks | Median OS was defined as the time from the beginning of study drug treatment until death due to any cause. |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of ADCT-502 (Total Antibody) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Area Under the Plasma Concentration Time Curve (AUC) of Drug To-antibody Ratio [DAR] ≥0 | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of PBD-conjugated Antibody (DAR ≥1) | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of Free Warhead SG3199 | Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose | — |
Countries
Belgium, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Dose 30μg/kg Dose-escalation part of the study. Participants received ADCT-502 (30 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 2 |
| Part 1: Dose 60μg/kg Dose-escalation part of the study. Participants received ADCT-502 (60 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 2 |
| Part 1: Dose 120μg/kg Dose-escalation part of the study. Participants received ADCT-502 (120 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 2 |
| Part 1: Dose 150μg/kg Dose-escalation part of the study. Participants received ADCT-502 (150 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 5 |
| Part 1: Dose 180μg/kg Dose-escalation part of the study. Participants received ADCT-502 (180 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 4 |
| Part 1: Dose 210μg/kg Dose-escalation part of the study. Participants received ADCT-502 (210 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 3 |
| Part 1: Dose 240μg/kg Dose-escalation part of the study. Participants received ADCT-502 (240 μg/kg) via a 1-hour intravenous infusion once every 3 weeks. | 3 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Clinical Progression | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Consent Withdrawn by Subject | 0 | 1 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 2 | 1 | 2 | 1 | 2 | 0 | 1 |
| Overall Study | Study Termination | 0 | 0 | 0 | 1 | 1 | 2 | 1 |
| Overall Study | Toxicity | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1: Dose 60μg/kg | Part 1: Dose 120μg/kg | Part 1: Dose 150μg/kg | Part 1: Dose 180μg/kg | Part 1: Dose 30μg/kg | Part 1: Dose 210μg/kg | Part 1: Dose 240μg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 13 Participants |
| Body Mass Index | 28.89 kg/m2 STANDARD_DEVIATION 16.514 | 26.94 kg/m2 STANDARD_DEVIATION 8.583 | 23.70 kg/m2 STANDARD_DEVIATION 2.218 | 30.33 kg/m2 STANDARD_DEVIATION 8.873 | 24.61 kg/m2 STANDARD_DEVIATION 0.059 | 23.89 kg/m2 STANDARD_DEVIATION 3.33 | 25.13 kg/m2 STANDARD_DEVIATION 2.762 | 26.03 kg/m2 STANDARD_DEVIATION 6.241 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 5 Participants | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 161.00 Centimetres STANDARD_DEVIATION 7.071 | 165.65 Centimetres STANDARD_DEVIATION 1.909 | 161.02 Centimetres STANDARD_DEVIATION 7.814 | 167.38 Centimetres STANDARD_DEVIATION 9.571 | 164.60 Centimetres STANDARD_DEVIATION 7.92 | 169.33 Centimetres STANDARD_DEVIATION 9.504 | 154.13 Centimetres STANDARD_DEVIATION 11.055 | 163.21 Centimetres STANDARD_DEVIATION 8.772 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 3 Participants | 2 Participants | 17 Participants |
| Region of Enrollment Belgium | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants | 3 participants | 2 participants | 2 participants | 3 participants | 18 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Weight | 76.85 Kilograms STANDARD_DEVIATION 49.427 | 73.65 Kilograms STANDARD_DEVIATION 21.85 | 61.70 Kilograms STANDARD_DEVIATION 9.113 | 84.25 Kilograms STANDARD_DEVIATION 22.422 | 66.75 Kilograms STANDARD_DEVIATION 6.576 | 67.93 Kilograms STANDARD_DEVIATION 2.173 | 59.90 Kilograms STANDARD_DEVIATION 10.3 | 69.69 Kilograms STANDARD_DEVIATION 18.222 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 5 | 0 / 4 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 2 / 2 | 5 / 5 | 4 / 4 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 2 | 1 / 2 | 0 / 2 | 2 / 5 | 1 / 4 | 2 / 3 | 1 / 3 |
Outcome results
Primary
Number of Participants Who Experience a Clinically Significant Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
Performance status was assessed using the ECOG performance status grades. These range between Grade 0 (fully active) and Grade 5 (dead). Clinical significance was determined by the investigator.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Primary
Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE)
An adverse event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| Part 1: Dose 60μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| Part 1: Dose 120μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 2 Participants |
| Part 1: Dose 150μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 5 Participants |
| Part 1: Dose 180μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 4 Participants |
| Part 1: Dose 210μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Part 1: Dose 240μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
Primary
Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE)
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 0 Participants |
| Part 1: Dose 60μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Part 1: Dose 120μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 0 Participants |
| Part 1: Dose 150μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Part 1: Dose 180μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Part 1: Dose 210μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Part 1: Dose 240μg/kg | Number of Participants Who Experience At Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
Primary
Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results
Standard 12-lead ECG's will be used. Clinical significance was determined by the investigator.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 0 Participants |
| Part 1: Dose 60μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 0 Participants |
| Part 1: Dose 120μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 1 Participants |
| Part 1: Dose 150μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 0 Participants |
| Part 1: Dose 180μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 1 Participants |
| Part 1: Dose 210μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 0 Participants |
| Part 1: Dose 240μg/kg | Number of Participants Who Experience Clinically Significant Electrocardiogram (ECG) Results | 0 Participants |
Primary
Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above
The Common Terminology Criteria For Adverse Events (CTCAE) Version 4 will be used.
Time frame: Day 1 to 3 Weeks (one cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 0 Participants |
| Part 1: Dose 60μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 0 Participants |
| Part 1: Dose 120μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 0 Participants |
| Part 1: Dose 150μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 0 Participants |
| Part 1: Dose 180μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 1 Participants |
| Part 1: Dose 210μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 0 Participants |
| Part 1: Dose 240μg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity With a CTCAE Grade of 3 or Above | 1 Participants |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities
Time frame: Day 1 to 3 Weeks (one cycle)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 0 Participants |
| Part 1: Dose 60μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 0 Participants |
| Part 1: Dose 120μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 0 Participants |
| Part 1: Dose 150μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 0 Participants |
| Part 1: Dose 180μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 1 Participants |
| Part 1: Dose 210μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 0 Participants |
| Part 1: Dose 240μg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities | 1 Participants |
Primary
Number of Participants With Clinically Significant Clinical Laboratory Tests
Clinical significance was determined by the investigator.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Primary
Number of Participants With Clinically Significant Physical Examination Results
Clinical significance was determined by the investigator.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Primary
Number of Participants With Clinically Significant Vital Signs
Vital sign measurements include arterial blood pressure, heart rate, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
Time frame: Day 1 to end of trial, a maximum of 168 days (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Dose 30μg/kg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part 1: Dose 60μg/kg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part 1: Dose 120μg/kg | Number of Participants With Clinically Significant Vital Signs | 1 Participants |
| Part 1: Dose 150μg/kg | Number of Participants With Clinically Significant Vital Signs | 1 Participants |
| Part 1: Dose 180μg/kg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
| Part 1: Dose 210μg/kg | Number of Participants With Clinically Significant Vital Signs | 2 Participants |
| Part 1: Dose 240μg/kg | Number of Participants With Clinically Significant Vital Signs | 0 Participants |
Secondary
Anti-drug Antibody (ADA) Titers to ADCT-502
Time frame: Blood sample collection before start of infusion in Cycles 1 and 2, and on Day 1 starting with Cycle 3 until disease progression, 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Area Under the Plasma Concentration Time Curve (AUC) of Drug To-antibody Ratio [DAR] ≥0
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of ADCT-502 (Total Antibody)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of Free Warhead SG3199
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) of PBD-conjugated Antibody (DAR ≥1)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Disease Control Rate (DCR)
DCR was defined as the number of participants with a best overall response of Complete Response (CR) or Partial Response (PR), or Stable Disease (SD). Analysis will be determined by the investigator per Response Evaluation In Solid Criteria (RECIST) version 1.1 criteria: stable disease is when the change is \> -30% and ≤ 20%, partial response is when there is a decrease in sum of target disease ≥ 30%, and complete response is when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.
Time frame: Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Dose 30μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 30μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 30μg/kg | Disease Control Rate (DCR) | Stable Disease | 2 Participants |
| Part 1: Dose 60μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 60μg/kg | Disease Control Rate (DCR) | Stable Disease | 1 Participants |
| Part 1: Dose 60μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 120μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 120μg/kg | Disease Control Rate (DCR) | Stable Disease | 0 Participants |
| Part 1: Dose 120μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 150μg/kg | Disease Control Rate (DCR) | Partial Response | 1 Participants |
| Part 1: Dose 150μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 150μg/kg | Disease Control Rate (DCR) | Stable Disease | 4 Participants |
| Part 1: Dose 180μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 180μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 180μg/kg | Disease Control Rate (DCR) | Stable Disease | 2 Participants |
| Part 1: Dose 210μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
| Part 1: Dose 210μg/kg | Disease Control Rate (DCR) | Stable Disease | 2 Participants |
| Part 1: Dose 210μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 240μg/kg | Disease Control Rate (DCR) | Stable Disease | 0 Participants |
| Part 1: Dose 240μg/kg | Disease Control Rate (DCR) | Partial Response | 0 Participants |
| Part 1: Dose 240μg/kg | Disease Control Rate (DCR) | Complete Response | 0 Participants |
Secondary
Duration of Response (DOR)
DOR was defined among responders (CR or 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.
Time frame: Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Maximum Observed Plasma Concentration (Cmax) for ADCT-502 (Total Antibody)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Maximum Observed Plasma Concentration (Cmax) for Drug To-antibody Ratio [DAR] ≥0
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Maximum Observed Plasma Concentration (Cmax) for Free Warhead SG3199
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Maximum Observed Plasma Concentration (Cmax) for PBD-conjugated Antibody (DAR ≥1)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Overall Response Rate (ORR)
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 discontinues ADCT-502. Analysis will be determined by the investigator per Response Evaluation In Solid Criteria (RECIST) version 1.1 criteria: partial response is when there is a decrease in sum of target disease ≥ 30%, and complete response is when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each.
Time frame: Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Dose 30μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Part 1: Dose 30μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 60μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 60μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Part 1: Dose 120μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 120μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Part 1: Dose 150μg/kg | Overall Response Rate (ORR) | Partial Response | 1 Participants |
| Part 1: Dose 150μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 180μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 180μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Part 1: Dose 210μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 210μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Part 1: Dose 240μg/kg | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| Part 1: Dose 240μg/kg | Overall Response Rate (ORR) | Partial Response | 0 Participants |
Secondary
Overall Survival (OS)
Median OS was defined as the time from the beginning of study drug treatment until death due to any cause.
Time frame: Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Progression-Free Survival (PFS)
PFS was defined among the efficacy population as the time from first dose of study drug until the first date of either disease progression or death due to any cause.
Time frame: Screening, day 1 of cycle 3 and cycle 5, then every 4 cycles, approximately every 12 weeks
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) for ADCT-502 (Total Antibody)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) for Drug To-antibody Ratio [DAR] ≥0)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) for Free Warhead SG3199
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.
Secondary
Time to Reach the Maximum Plasma Concentration (Tmax) for PBD-conjugated Antibody (DAR ≥1)
Time frame: Before infusion, End of Infusion, and 1, 3, 6, 24, 48, 96, 168 and 336 hours post infusion for Cycle 1 & 2. Before infusion and end of infusion of Cycle 3 to disease progression, and 30 days and 12 weeks after last dose
Population: This analysis was planned but data was not collected as the study was terminated due to safety reasons.