Burkitt's Lymphoma, Chronic Lymphocytic Leukemia, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, Marginal Zone, Non-Hodgkin Lymphoma, Primary Mediastinal B-cell Lymphoma, Waldenstrom Macroglobulinemia
Conditions
Keywords
Loncastuximab tesirine
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.
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.
Interventions
DRUGADCT-402
intravenous infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Italy, United Kingdom, United States
Participant flow
Pre-assignment details
Participants were screened at 11 sites in 3 countries.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: 15 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (15 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 4 |
| Part 1: 30 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (30 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 4 |
| Part 1: 60 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (60 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 4 |
| Part 1: 90 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (90 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 5 |
| Part 1: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 16 |
| Part 2: 120 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (120 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 26 |
| Part 1: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 19 |
| Part 2: 150 μg/kg Q3W Participants received an intravenous (IV) infusion of ADCT-402 (150 μg/kg) on Day 1 of each 3 week cycle (Q3W). | 69 |
| Part 1: 200 μg/kg Q3W and Q6W 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). | 36 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 2 | 3 | 8 | 18 | 10 | 47 | 20 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Miscellaneous | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 13 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | 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: 15 μg/kg Q3W | Part 1: 150 μg/kg Q3W | Part 2: 150 μg/kg Q3W | Part 1: 200 μg/kg Q3W and Q6W | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 3 Participants | 13 Participants | 12 Participants | 3 Participants | 6 Participants | 26 Participants | 17 Participants | 84 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 14 Participants | 1 Participants | 13 Participants | 43 Participants | 19 Participants | 99 Participants |
| Age, Continuous | 68.3 years STANDARD_DEVIATION 11.53 | 51.3 years STANDARD_DEVIATION 18.82 | 68.2 years STANDARD_DEVIATION 12.38 | 71.0 years STANDARD_DEVIATION 10.2 | 63.7 years STANDARD_DEVIATION 13.37 | 72.5 years STANDARD_DEVIATION 8.39 | 58.5 years STANDARD_DEVIATION 13.96 | 58.7 years STANDARD_DEVIATION 15.82 | 61.7 years STANDARD_DEVIATION 12.82 | 61.7 years STANDARD_DEVIATION 14.49 |
| Body Mass Index (BMI) | 26.60 kg/m^2 STANDARD_DEVIATION 5.466 | 25.89 kg/m^2 STANDARD_DEVIATION 5.428 | 30.77 kg/m^2 STANDARD_DEVIATION 8.931 | 29.40 kg/m^2 STANDARD_DEVIATION 6.882 | 26.68 kg/m^2 STANDARD_DEVIATION 5.458 | 25.21 kg/m^2 STANDARD_DEVIATION 3.971 | 29.57 kg/m^2 STANDARD_DEVIATION 5.575 | 26.62 kg/m^2 STANDARD_DEVIATION 6.648 | 30.15 kg/m^2 STANDARD_DEVIATION 7.235 | 27.93 kg/m^2 STANDARD_DEVIATION 6.587 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0: Fully Active | 0 Participants | 2 Participants | 0 Participants | 7 Participants | 7 Participants | 2 Participants | 4 Participants | 20 Participants | 12 Participants | 54 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1: Restricted in Physical Activity; Ambulatory | 3 Participants | 2 Participants | 4 Participants | 8 Participants | 19 Participants | 1 Participants | 12 Participants | 36 Participants | 21 Participants | 106 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2: Ambulatory and Capable of All Self-care | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 12 Participants | 3 Participants | 21 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3: Capable of Only Limited Self-care | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4: Completely Disabled | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 5: Dead | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 5 Participants | 16 Participants | 25 Participants | 4 Participants | 18 Participants | 65 Participants | 35 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Height | 170.73 cm STANDARD_DEVIATION 12.545 | 173.65 cm STANDARD_DEVIATION 11.544 | 167.68 cm STANDARD_DEVIATION 10.275 | 170.72 cm STANDARD_DEVIATION 8.977 | 171.47 cm STANDARD_DEVIATION 9.79 | 172.23 cm STANDARD_DEVIATION 18.438 | 172.79 cm STANDARD_DEVIATION 10.584 | 170.56 cm STANDARD_DEVIATION 11.908 | 171.29 cm STANDARD_DEVIATION 12.193 | 171.11 cm STANDARD_DEVIATION 11.221 |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 5 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 4 Participants | 4 Participants | 4 Participants | 14 Participants | 19 Participants | 4 Participants | 19 Participants | 61 Participants | 35 Participants | 164 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 7 Participants | 2 Participants | 6 Participants | 34 Participants | 10 Participants | 69 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 13 Participants | 19 Participants | 2 Participants | 13 Participants | 35 Participants | 26 Participants | 114 Participants |
| Weight | 78.73 kg STANDARD_DEVIATION 25.445 | 79.95 kg STANDARD_DEVIATION 26.942 | 86.38 kg STANDARD_DEVIATION 23.597 | 86.89 kg STANDARD_DEVIATION 25.996 | 78.66 kg STANDARD_DEVIATION 18.113 | 73.65 kg STANDARD_DEVIATION 7.204 | 88.67 kg STANDARD_DEVIATION 20.82 | 77.87 kg STANDARD_DEVIATION 22.453 | 88.71 kg STANDARD_DEVIATION 24.834 | 82.23 kg STANDARD_DEVIATION 22.635 |
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 | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 2 / 4 | 2 / 4 | 3 / 5 | 8 / 16 | 18 / 26 | 10 / 19 | 47 / 69 | 20 / 36 |
| other Total, other adverse events | 4 / 4 | 3 / 4 | 4 / 4 | 5 / 5 | 16 / 16 | 25 / 26 | 19 / 19 | 65 / 69 | 36 / 36 |
| serious Total, serious adverse events | 1 / 4 | 1 / 4 | 0 / 4 | 4 / 5 | 4 / 16 | 4 / 26 | 6 / 19 | 40 / 69 | 15 / 36 |
Outcome results
Primary
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
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)
Population: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 4 Participants |
| Part 1: 30 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| Part 1: 60 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 4 Participants |
| Part 1: 90 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 5 Participants |
| Part 1: 120 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 16 Participants |
| Part 1: 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 26 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 19 Participants |
| Part 2: 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 68 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 36 Participants |
Primary
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
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)
Population: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Part 1: 30 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Part 1: 60 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 0 Participants |
| Part 1: 90 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 4 Participants |
| Part 1: 120 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 4 Participants |
| Part 1: 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 14 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 6 Participants |
| Part 2: 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 40 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 15 Participants |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
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)
Population: All participants in Part 1 who completed at least one cycle of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: 30 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: 60 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: 90 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Part 1: 120 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: 150 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 2 Participants |
Primary
Recommended Dose of ADCT-402 for Part 2
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)
Population: All participants in Part 1 who completed at least one cycle of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Recommended Dose of ADCT-402 for Part 2 | Recommended Part 2 Dose 1 | 120 μg/kg |
| Part 1: 15 μg/kg Q3W | Recommended Dose of ADCT-402 for Part 2 | Recommended Part 2 Dose 2 | 150 μg/kg |
Secondary
Accumulation Index (AI) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.12 ratio | Standard Deviation 0.173 |
| Part 1: 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.15 ratio | Standard Deviation 0.229 |
| Part 1: 30 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.37 ratio | Standard Deviation 0.264 |
| Part 1: 30 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.35 ratio | Standard Deviation 0.252 |
| Part 1: 60 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.70 ratio | Standard Deviation 0.467 |
| Part 1: 60 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.71 ratio | Standard Deviation 0.325 |
| Part 1: 90 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.42 ratio | Standard Deviation 0.399 |
| Part 1: 90 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.80 ratio | Standard Deviation 0.962 |
| Part 1: 120 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.47 ratio | Standard Deviation 0.369 |
| Part 1: 120 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.62 ratio | Standard Deviation 0.492 |
| Part 1: 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.46 ratio | Standard Deviation 0.368 |
| Part 1: 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.63 ratio | Standard Deviation 0.486 |
| Part 1: 200 μg/kg Q3W and Q6W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.78 ratio | Standard Deviation 0.418 |
| Part 1: 200 μg/kg Q3W and Q6W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.76 ratio | Standard Deviation 0.385 |
| Part 2: 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.23 ratio | Standard Deviation 0.16 |
| Part 2: 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 | total Ab: Cycle 2 | 1.36 ratio | Standard Deviation 0.314 |
Secondary
Apparent Clearance (CL) at Steady State for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 1.28 liters/day | — |
| Part 1: 15 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1.78 liters/day | Standard Deviation 1.8 |
| Part 1: 15 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 2.49 liters/day | Standard Deviation 0.978 |
| Part 1: 15 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 1.76 liters/day | Standard Deviation 1.71 |
| Part 1: 30 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.646 liters/day | Standard Deviation 0.348 |
| Part 1: 30 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 0.577 liters/day | Standard Deviation 0.309 |
| Part 1: 30 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 1.08 liters/day | Standard Deviation 0.164 |
| Part 1: 60 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 38.1 liters/day | Standard Deviation 65.5 |
| Part 1: 60 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.696 liters/day | Standard Deviation 0.444 |
| Part 1: 60 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.415 liters/day | Standard Deviation 0.205 |
| Part 1: 90 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 0.640 liters/day | — |
| Part 1: 90 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 7.13 liters/day | Standard Deviation 8.91 |
| Part 1: 90 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 19.6 liters/day | Standard Deviation 40.6 |
| Part 1: 90 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 1.42 liters/day | Standard Deviation 2.06 |
| Part 1: 120 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 2.47 liters/day | Standard Deviation 5 |
| Part 1: 120 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 0.581 liters/day | Standard Deviation 0.66 |
| Part 1: 120 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 2.09 liters/day | Standard Deviation 4.07 |
| Part 1: 120 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 17.8 liters/day | Standard Deviation 109 |
| Part 1: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | SG3199: Cycle 1 | 627 liters/day | — |
| Part 1: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3.84 liters/day | Standard Deviation 8.53 |
| Part 1: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.986 liters/day | Standard Deviation 2.48 |
| Part 1: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 3.87 liters/day | Standard Deviation 8.95 |
| Part 1: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 1.05 liters/day | Standard Deviation 2.91 |
| Part 1: 200 μg/kg Q3W and Q6W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 7.12 liters/day | Standard Deviation 9.62 |
| Part 1: 200 μg/kg Q3W and Q6W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.407 liters/day | Standard Deviation 0.143 |
| Part 1: 200 μg/kg Q3W and Q6W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3.11 liters/day | Standard Deviation 5.3 |
| Part 1: 200 μg/kg Q3W and Q6W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 0.417 liters/day | Standard Deviation 0.161 |
| Part 2: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 2 | 0.323 liters/day | Standard Deviation 0.187 |
| Part 2: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.349 liters/day | Standard Deviation 0.21 |
| Part 2: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | total Ab: Cycle 1 | 2.02 liters/day | Standard Deviation 5.11 |
| Part 2: 150 μg/kg Q3W | Apparent Clearance (CL) at Steady State for ADCT-402 | PBD conjugated Ab: Cycle 1 | 12.6 liters/day | Standard Deviation 39.4 |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 432 day*ng/mL | Standard Deviation 173 |
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 869 day*ng/mL | — |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 2001 day*ng/mL | Standard Deviation 663 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 5333 day*ng/mL | Standard Deviation 4002 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 5622 day*ng/mL | Standard Deviation 7170 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 16409 day*ng/mL | — |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 13292 day*ng/mL | Standard Deviation 8495 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 10232 day*ng/mL | Standard Deviation 6220 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | SG3199: Cycle 1 | 0.154 day*ng/mL | — |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 11498 day*ng/mL | Standard Deviation 8175 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 12692 day*ng/mL | Standard Deviation 8968 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 29174 day*ng/mL | Standard Deviation 25838 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 38991 day*ng/mL | Standard Deviation 53597 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | total Ab: Cycle 1 | 43952 day*ng/mL | Standard Deviation 24032 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 32629 day*ng/mL | Standard Deviation 19488 |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 2285 day*ng/mL | Standard Deviation 2928 |
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 2636 day*ng/mL | Standard Deviation 3387 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 4662 day*ng/mL | Standard Deviation 2096 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 3458 day*ng/mL | Standard Deviation 1426 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 10575 day*ng/mL | Standard Deviation 1121 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 10211 day*ng/mL | Standard Deviation 8827 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 17141 day*ng/mL | Standard Deviation 15029 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 10171 day*ng/mL | Standard Deviation 11244 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 24247 day*ng/mL | Standard Deviation 10902 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 19890 day*ng/mL | Standard Deviation 8968 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 22859 day*ng/mL | Standard Deviation 12080 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 28041 day*ng/mL | Standard Deviation 15312 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 46469 day*ng/mL | Standard Deviation 12675 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 39362 day*ng/mL | Standard Deviation 9800 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 2 | 48524 day*ng/mL | Standard Deviation 28858 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 38466 day*ng/mL | Standard Deviation 23514 |
| Unknown | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | SG3199: Cycle 2 | — day*ng/mL | — |
| Unknown | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | SG3199: Cycle 1 | — day*ng/mL | — |
| Unknown | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | total Ab: Cycle 1 | — day*ng/mL | — |
| Unknown | Area Under the Serum Concentration-Time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-402 | PBD conjugated Ab: Cycle 1 | — day*ng/mL | — |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 1063 day*ng/mL | Standard Deviation 1340 |
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 1924 day*ng/mL | Standard Deviation 2576 |
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 1185 day*ng/mL | Standard Deviation 1540 |
| Part 1: 15 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1933 day*ng/mL | Standard Deviation 2289 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 3194 day*ng/mL | Standard Deviation 1136 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 2955 day*ng/mL | Standard Deviation 1132 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 2390 day*ng/mL | Standard Deviation 826 |
| Part 1: 30 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 3986 day*ng/mL | Standard Deviation 1725 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 5573 day*ng/mL | Standard Deviation 4827 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3875 day*ng/mL | Standard Deviation 3228 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 5032 day*ng/mL | Standard Deviation 4334 |
| Part 1: 60 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 7958 day*ng/mL | Standard Deviation 6882 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 10369 day*ng/mL | Standard Deviation 11656 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 8869 day*ng/mL | Standard Deviation 9108 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 6587 day*ng/mL | Standard Deviation 6842 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 14025 day*ng/mL | Standard Deviation 15704 |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 1 | 0.00213 day*ng/mL | — |
| Part 1: 90 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 2 | 0.0242 day*ng/mL | Standard Deviation 0.0234 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 15980 day*ng/mL | Standard Deviation 7649 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 1 | 0.00462 day*ng/mL | Standard Deviation 0.00671 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 18707 day*ng/mL | Standard Deviation 10505 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 13544 day*ng/mL | Standard Deviation 7503 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 2 | 0.154 day*ng/mL | Standard Deviation 0.286 |
| Part 1: 120 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 23428 day*ng/mL | Standard Deviation 13513 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 2 | 0.0108 day*ng/mL | Standard Deviation 0.0248 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 1 | 0.0222 day*ng/mL | Standard Deviation 0.0423 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 28657 day*ng/mL | Standard Deviation 19457 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 16973 day*ng/mL | Standard Deviation 9745 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 23109 day*ng/mL | Standard Deviation 15370 |
| Part 1: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 14258 day*ng/mL | Standard Deviation 8248 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 57450 day*ng/mL | Standard Deviation 26899 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 33834 day*ng/mL | Standard Deviation 14888 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 2 | 0.00425 day*ng/mL | Standard Deviation 0.00461 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 1 | 0.0174 day*ng/mL | Standard Deviation 0.0303 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 48183 day*ng/mL | Standard Deviation 20288 |
| Part 1: 200 μg/kg Q3W and Q6W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 30571 day*ng/mL | Standard Deviation 12425 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 1 | 0.0436 day*ng/mL | Standard Deviation 0.0959 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | SG3199: Cycle 2 | 0.00332 day*ng/mL | Standard Deviation 0.00215 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 1 | 36099 day*ng/mL | Standard Deviation 20829 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 30386 day*ng/mL | Standard Deviation 16960 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | total Ab: Cycle 2 | 49892 day*ng/mL | Standard Deviation 31012 |
| Part 2: 150 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 39609 day*ng/mL | Standard Deviation 24852 |
Secondary
Duration of Response (DoR)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Duration of Response (DoR) | 5.36 months |
Secondary
Maximum Observed Serum Concentration (Cmax) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 260 ng/mL | Standard Deviation 85.5 |
| Part 1: 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 447 ng/mL | Standard Deviation 283 |
| Part 1: 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 298 ng/mL | Standard Deviation 83.7 |
| Part 1: 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 398 ng/mL | Standard Deviation 284 |
| Part 1: 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 542 ng/mL | Standard Deviation 192 |
| Part 1: 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1971 ng/mL | Standard Deviation 2566 |
| Part 1: 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 404 ng/mL | Standard Deviation 161 |
| Part 1: 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 2906 ng/mL | Standard Deviation 4034 |
| Part 1: 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 864 ng/mL | Standard Deviation 686 |
| Part 1: 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 721 ng/mL | Standard Deviation 481 |
| Part 1: 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 856 ng/mL | Standard Deviation 475 |
| Part 1: 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 1275 ng/mL | Standard Deviation 1025 |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 1416 ng/mL | Standard Deviation 799 |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 1560 ng/mL | Standard Deviation 1102 |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 1088 ng/mL | Standard Deviation 748 |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 2422 ng/mL | Standard Deviation 983 |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 1 | 0.102 ng/mL | — |
| Part 1: 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 2 | 0.0704 ng/mL | Standard Deviation 0.0152 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 2829 ng/mL | Standard Deviation 1257 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 1 | 0.0372 ng/mL | Standard Deviation 0.0208 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 2573 ng/mL | Standard Deviation 655 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 2374 ng/mL | Standard Deviation 1040 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 2 | 0.0403 ng/mL | Standard Deviation 0.0116 |
| Part 1: 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 3142 ng/mL | Standard Deviation 888 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 2 | 0.0485 ng/mL | Standard Deviation 0.0449 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 1 | 0.0570 ng/mL | Standard Deviation 0.0454 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 4798 ng/mL | Standard Deviation 3334 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 4383 ng/mL | Standard Deviation 4460 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 3776 ng/mL | Standard Deviation 2738 |
| Part 1: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3416 ng/mL | Standard Deviation 3093 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 5059 ng/mL | Standard Deviation 1027 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 4185 ng/mL | Standard Deviation 1308 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 2 | 0.0293 ng/mL | Standard Deviation 0.00329 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 1 | 0.0479 ng/mL | Standard Deviation 0.0381 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 4293 ng/mL | Standard Deviation 1021 |
| Part 1: 200 μg/kg Q3W and Q6W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3619 ng/mL | Standard Deviation 688 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 1 | 0.0468 ng/mL | Standard Deviation 0.0333 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | SG3199: Cycle 2 | 0.0516 ng/mL | Standard Deviation 0.0325 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 1 | 4543 ng/mL | Standard Deviation 1805 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 3798 ng/mL | Standard Deviation 1332 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | total Ab: Cycle 2 | 3834 ng/mL | Standard Deviation 1913 |
| Part 2: 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 3178 ng/mL | Standard Deviation 1733 |
Secondary
Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402
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)
Population: All participants who were tested for ADA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA at anytime | 6 Participants |
| Part 1: 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA pre-dose | 5 Participants |
| Part 1: 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA post-dose only | 1 Participants |
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 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)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Overall Response Rate (ORR) | 1 Participants |
| Part 1: 30 μg/kg Q3W | Overall Response Rate (ORR) | 1 Participants |
| Part 1: 60 μg/kg Q3W | Overall Response Rate (ORR) | 1 Participants |
| Part 1: 90 μg/kg Q3W | Overall Response Rate (ORR) | 2 Participants |
| Part 1: 120 μg/kg Q3W | Overall Response Rate (ORR) | 9 Participants |
| Part 1: 150 μg/kg Q3W | Overall Response Rate (ORR) | 11 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Overall Response Rate (ORR) | 12 Participants |
| Part 2: 150 μg/kg Q3W | Overall Response Rate (ORR) | 25 Participants |
| Part 1: 200 μg/kg Q3W and Q6W | Overall Response Rate (ORR) | 20 Participants |
Secondary
Overall Survival (OS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Overall Survival (OS) | 8.25 months |
Secondary
Progression-free Survival (PFS)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: 15 μg/kg Q3W | Progression-free Survival (PFS) | 3.09 months |
Secondary
Terminal Half-life (Thalf) of ADCT-402
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 3.98 days |
| Part 1: 15 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 2.75 days |
| Part 1: 15 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 3.71 days |
| Part 1: 15 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 1.15 days |
| Part 1: 30 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 6.84 days |
| Part 1: 30 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 10.1 days |
| Part 1: 30 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 9.58 days |
| Part 1: 60 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 6.30 days |
| Part 1: 60 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 16.3 days |
| Part 1: 60 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 16.5 days |
| Part 1: 90 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 8.82 days |
| Part 1: 90 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 11.4 days |
| Part 1: 90 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 13.4 days |
| Part 1: 90 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 3.97 days |
| Part 1: 120 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 14.9 days |
| Part 1: 120 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 6.33 days |
| Part 1: 120 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 12.5 days |
| Part 1: 120 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 7.00 days |
| Part 1: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 6.58 days |
| Part 1: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 6.43 days |
| Part 1: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 11.6 days |
| Part 1: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 14.3 days |
| Part 1: 200 μg/kg Q3W and Q6W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 16.3 days |
| Part 1: 200 μg/kg Q3W and Q6W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 9.39 days |
| Part 1: 200 μg/kg Q3W and Q6W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 7.96 days |
| Part 1: 200 μg/kg Q3W and Q6W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 14.7 days |
| Part 2: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 2 | 18.4 days |
| Part 2: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 1 | 10.4 days |
| Part 2: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | PBD conjugated Ab: Cycle 2 | 15.5 days |
| Part 2: 150 μg/kg Q3W | Terminal Half-life (Thalf) of ADCT-402 | total Ab: Cycle 1 | 12.7 days |
Secondary
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0837 days |
| Part 1: 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0649 days |
| Part 1: 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0844 days |
| Part 1: 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.122 days |
| Part 1: 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0833 days |
| Part 1: 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0618 days |
| Part 1: 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0833 days |
| Part 1: 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0618 days |
| Part 1: 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0417 days |
| Part 1: 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0819 days |
| Part 1: 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0833 days |
| Part 1: 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0417 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0833 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0500 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0500 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0833 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 1 | 0.0833 days |
| Part 1: 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 2 | 1.05 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0833 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 1 | 0.0854 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0830 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0833 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 2 | 0.120 days |
| Part 1: 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0632 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 2 | 0.0632 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 1 | 0.0844 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0639 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0837 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0642 days |
| Part 1: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0840 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.132 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0840 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 2 | 0.165 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 1 | 0.128 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0854 days |
| Part 1: 200 μg/kg Q3W and Q6W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0858 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 1 | 0.165 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | SG3199: Cycle 2 | 0.162 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 1 | 0.0837 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 0.0840 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | total Ab: Cycle 2 | 0.0858 days |
| Part 2: 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 0.0826 days |
Secondary
Volume of Distribution at Steady State (Vss) for ADCT-402
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: 15 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 4.71 liters | — |
| Part 1: 15 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 3.82 liters | Standard Deviation 1.25 |
| Part 1: 15 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 4.47 liters | Standard Deviation 0.759 |
| Part 1: 15 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 3.83 liters | Standard Deviation 0.854 |
| Part 1: 30 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 10.1 liters | Standard Deviation 8.57 |
| Part 1: 30 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 9.62 liters | Standard Deviation 8.54 |
| Part 1: 30 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 10.3 liters | Standard Deviation 4.83 |
| Part 1: 60 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 7.30 liters | Standard Deviation 1.38 |
| Part 1: 60 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 4.96 liters | Standard Deviation 0.318 |
| Part 1: 60 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 8.29 liters | Standard Deviation 0.54 |
| Part 1: 90 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 7.84 liters | — |
| Part 1: 90 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 9.68 liters | Standard Deviation 2.68 |
| Part 1: 90 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 7.62 liters | Standard Deviation 1.09 |
| Part 1: 90 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 8.52 liters | Standard Deviation 1.34 |
| Part 1: 120 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 5.51 liters | Standard Deviation 1.29 |
| Part 1: 120 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 8.11 liters | Standard Deviation 4.57 |
| Part 1: 120 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 5.95 liters | Standard Deviation 1.86 |
| Part 1: 120 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 6.71 liters | Standard Deviation 3.13 |
| Part 1: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | SG3199: Cycle 1 | 335 liters | — |
| Part 1: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 7.59 liters | Standard Deviation 6.18 |
| Part 1: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 7.48 liters | Standard Deviation 4.29 |
| Part 1: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 6.60 liters | Standard Deviation 3.16 |
| Part 1: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 8.21 liters | Standard Deviation 3.64 |
| Part 1: 200 μg/kg Q3W and Q6W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 7.91 liters | Standard Deviation 0.0252 |
| Part 1: 200 μg/kg Q3W and Q6W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 9.18 liters | Standard Deviation 3.43 |
| Part 1: 200 μg/kg Q3W and Q6W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 11.5 liters | Standard Deviation 11.1 |
| Part 1: 200 μg/kg Q3W and Q6W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 9.46 liters | Standard Deviation 5.26 |
| Part 2: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 2 | 6.86 liters | Standard Deviation 2.27 |
| Part 2: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 2 | 6.21 liters | Standard Deviation 1.7 |
| Part 2: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | total Ab: Cycle 1 | 7.20 liters | Standard Deviation 2.03 |
| Part 2: 150 μg/kg Q3W | Volume of Distribution at Steady State (Vss) for ADCT-402 | PBD conjugated Ab: Cycle 1 | 7.18 liters | Standard Deviation 2.52 |