Acute Lymphoblastic Leukemia
Conditions
Keywords
Loncastuximab tesirine
Brief summary
This study evaluates ADCT-402 in participants with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL). 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-402-102 is the first clinical study with ADCT-402 in participants with B-cell lineage acute lymphoblastic leukemia (B-ALL). 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 an infusion of ADCT-402 either on weekly administration or every 3-week administration. participants on weekly administration will receive an infusion of ADCT-402 on Days 1, 8, and 15 of each 3 week treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-402 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined. In Part 2 (expansion), all participants will be assigned to the recommended dose and/or schedule of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee. For each patient, 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 patient 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 patient treated to last patient 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
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, ages 12 years and older, with relapsed or refractory B-ALL who have failed, or are intolerant to, any established therapy; or for whom no other treatment options are available. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Serum/plasma creatinine ≤1.5mg/dL. * Serum/plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement. * Total serum/plasma bilirubin ≤1.5 times ULN. * White Blood Cell Count value of \<15,000 cells/μL prior to Cycle 1 Day 1. * Negative urine or serum beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to the Cycle 1, Day 1 visit, for women of childbearing potential. * Males, and female patients who are biologically capable of having children, must agree to use a medically acceptable method of birth control.
Exclusion criteria
* Patients who have an option for other treatment for B-ALL at the current state of disease. * Known active central nervous system (CNS) leukemia. * Patients with Burkitt's leukemia/lymphoma. * Active graft-versus-host disease. * Autologous or allogenic transplant within the 60 days prior to Screening. * Known history of immunogenicity or hypersensitivity to a CD19 antibody. * Known history of positive serum human ADA. * Active autoimmune disease, motor neuropathy considered of autoimmune origin, or other central nervous system autoimmune disease. * Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV). * History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome. * Pregnant or breastfeeding women. * Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \>115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias. * Use of any other experimental medication(s) within 14 days or 5 half-lives, but in no case \<14 days prior to the start of treatment on Cycle 1, Day 1, except if approved by the Sponsor. * Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea,steroids and any targeted small molecules or biologics), or radiotherapy, within 14 days or 5 half-lives (whichever is shorter) prior to the Cycle 1, Day 1 treatment, except if approved by the Sponsor. * Failure to recover from acute non hematologic toxicity (except alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening. * Isolated extramedullary relapse. * Congenital long QT syndrome or a corrected QTc interval of ≥450 ms at the Screening visit. * Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy determined not be exclusionary. * Any other significant medical illness, abnormality, or condition that would make the patient inappropriate for study participation or put the patient at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | Day 1 to End of Cycle 1 (3 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: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome (Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage). * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration. |
| Recommended Dose of ADCT-402 for Part 2 | Day 1 to End of Cycle 1 (3 weeks) | The recommended dose was to be 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) | From first dose of study drug up to 12 weeks after last dose (up to 39 weeks) | 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) | From first dose of study drug up to 12 weeks after last dose (up to 39 weeks) | 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 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUC∞ for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Weekly (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUC∞ for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. AI is the ratio of AUC 0-24 after multiple doses versus a single dose. It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. |
| Overall Response Rate (ORR) | From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug | ORR is defined as the number of participants with a best overall response of complete response (CR), complete response with incomplete blood count recovery (Cri) or partial response (PR) at the time each participant discontinues treatment with ADCT-402. CR is defined as achieving each of the following: * Bone marrow differential showing ≤5% blast cells. * Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Absence of extramedullary disease. * Participant is independent of red blood cell transfusions. Cri is defined as achieving all CR criteria except that values for ANC may be \<1.0 x 10\^9/L and/or values for platelets may be \<100 x 10\^9/L. PR is defined as achieving each of the following: * ANC ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level \>5% and ≤25%, or bone marrow differential showing \<5% blast cells. |
| Volume of Distribution at Steady State for ADCT-402 | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | — |
| Mean Residence Time for ADCT-402 | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | — |
| Terminal Elimination Phase Rate Constant for ADCT-402 | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | — |
| Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | T1/2 for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | T1/2 for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Apparent clearance for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Apparent clearance for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Vd beta for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. |
| Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every Week (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Vd beta for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. |
| Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | Blood serum samples were collected and analysed to determine the presence or absence of ADA. |
| Accumulation Index (AI) for ADCT-402 Administered Weekly (QW) | Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2 | AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. AI is the ratio of AUC 0-24 after multiple doses versus a single dose. It is the increase in drug plasma concentration after multiple dosing until a steady state is reached. |
| Duration of Response | From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug | Duration of response is defined among responders (complete response \[CR\], complete response with incomplete blood count recovery \[Cri\], 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. Disease progression is defined as: * For participants with CR or CRi, the first date of reappearance of blast cells in bone marrow and/or peripheral blood to a level ≥5%, or development of extramedullary disease. * For participants with PR, the first date of an increase in blast cells in bone marrow and/or peripheral blood such that the patient does not continue to meet the criteria for PR. |
| Overall Survival | From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug | Overall survival is defined as the time from the first dose of study drug treatment until the date of death due to any cause. |
| Progression-free Survival | From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug | Progression-free survival is 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 15 μg/kg Q3W Participants received 15 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 5 |
| 30 μg/kg Q3W Participants received 30 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 7 |
| 60 μg/kg Q3W Participants received 60 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 3 |
| 90 μg/kg Q3W Participants received 90 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 4 |
| 120 μg/kg Q3W Participants received 120 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 5 |
| 150 μg/kg Q3W Participants received 150 μg/kg ADCT-402 on Day 1 of each 3-week treatment cycle. | 6 |
| 50 μg/kg QW Participants received 50 μg/kg ADCT-402 on Days 1, 8 and 15 of each 3-week (21-day) treatment cycle. This dose level for the QW dosing was based on the safety and tolerability of participants who have been treated on the every 3-week (Q3W) schedule. | 5 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 5 | 5 | 3 | 3 | 3 | 6 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Miscellaneous | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 30 μg/kg Q3W | 60 μg/kg Q3W | 90 μg/kg Q3W | 120 μg/kg Q3W | 15 μg/kg Q3W | 150 μg/kg Q3W | 50 μg/kg QW | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 21.95 | 50.3 years STANDARD_DEVIATION 6.51 | 63.8 years STANDARD_DEVIATION 7.09 | 46.8 years STANDARD_DEVIATION 18.14 | 43.6 years STANDARD_DEVIATION 21.22 | 45.2 years STANDARD_DEVIATION 19.61 | 42.8 years STANDARD_DEVIATION 24.3 | 48.3 years STANDARD_DEVIATION 18.66 |
| Body Mass Index (BMI) | 34.05 kg/m^2 STANDARD_DEVIATION 13.059 | 30.43 kg/m^2 STANDARD_DEVIATION 3.504 | 21.07 kg/m^2 STANDARD_DEVIATION 3.356 | 26.22 kg/m^2 STANDARD_DEVIATION 2.949 | 28.62 kg/m^2 STANDARD_DEVIATION 7.192 | 32.70 kg/m^2 STANDARD_DEVIATION 12.605 | 27.93 kg/m^2 STANDARD_DEVIATION 5.741 | 29.15 kg/m^2 STANDARD_DEVIATION 9.142 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status | 1.29 Score on a scale STANDARD_DEVIATION 0.488 | 0.67 Score on a scale STANDARD_DEVIATION 0.577 | 1.50 Score on a scale STANDARD_DEVIATION 0.577 | 1.60 Score on a scale STANDARD_DEVIATION 0.548 | 1.00 Score on a scale STANDARD_DEVIATION 0 | 1.33 Score on a scale STANDARD_DEVIATION 1.033 | 1.40 Score on a scale STANDARD_DEVIATION 0.548 | 1.29 Score on a scale STANDARD_DEVIATION 0.622 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 1 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 | 167.97 cm STANDARD_DEVIATION 17.05 | 162.60 cm STANDARD_DEVIATION 0 | 164.78 cm STANDARD_DEVIATION 11.943 | 172.32 cm STANDARD_DEVIATION 10.146 | 162.40 cm STANDARD_DEVIATION 8.51 | 163.58 cm STANDARD_DEVIATION 7.398 | 155.75 cm STANDARD_DEVIATION 5.072 | 164.83 cm STANDARD_DEVIATION 11.211 |
| 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 7 Participants | 1 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 27 Participants |
| Region of Enrollment United States | 7 Participants | 3 Participants | 4 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 35 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 19 Participants |
| Weight | 93.80 kg STANDARD_DEVIATION 31.551 | 87.13 kg STANDARD_DEVIATION 13.301 | 58.33 kg STANDARD_DEVIATION 15.745 | 78.00 kg STANDARD_DEVIATION 11.663 | 76.44 kg STANDARD_DEVIATION 26.043 | 83.05 kg STANDARD_DEVIATION 38.842 | 70.58 kg STANDARD_DEVIATION 11.576 | 79.28 kg STANDARD_DEVIATION 25.631 |
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 | 5 / 5 | 5 / 7 | 3 / 3 | 3 / 4 | 3 / 5 | 6 / 6 | 3 / 5 |
| other Total, other adverse events | 5 / 5 | 7 / 7 | 3 / 3 | 4 / 4 | 5 / 5 | 6 / 6 | 5 / 5 |
| serious Total, serious adverse events | 5 / 5 | 4 / 7 | 2 / 3 | 3 / 4 | 5 / 5 | 5 / 6 | 4 / 5 |
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: From first dose of study drug up to 12 weeks after last dose (up to 39 weeks)
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 5 Participants |
| 30 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 7 Participants |
| 60 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 3 Participants |
| 90 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 4 Participants |
| 120 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 5 Participants |
| 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 6 Participants |
| 50 μg/kg QW | Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE) | 5 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: From first dose of study drug up to 12 weeks after last dose (up to 39 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 5 Participants |
| 30 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 4 Participants |
| 60 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| 90 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 3 Participants |
| 120 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 5 Participants |
| 150 μg/kg Q3W | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 5 Participants |
| 50 μg/kg QW | Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE) | 4 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: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome (Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage). * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration.
Time frame: Day 1 to End of Cycle 1 (3 weeks)
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 30 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 60 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 90 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 120 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| 150 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
| 50 μg/kg QW | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
Primary
Recommended Dose of ADCT-402 for Part 2
The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.
Time frame: Day 1 to End of Cycle 1 (3 weeks)
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W)
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts. AI is the ratio of AUC 0-24 after multiple doses versus a single dose. It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.04 ratio | — |
| 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.01 ratio | — |
| 30 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.62 ratio | Standard Deviation 0.433 |
| 30 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.14 ratio | Standard Deviation 0.242 |
| 60 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.00 ratio | — |
| 60 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.00 ratio | — |
| 90 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.08 ratio | — |
| 90 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.06 ratio | — |
| 120 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.30 ratio | Standard Deviation 0.509 |
| 120 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.67 ratio | Standard Deviation 0.939 |
| 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.06 ratio | Standard Deviation 0.0532 |
| 150 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.03 ratio | Standard Deviation 0.0187 |
Secondary
Accumulation Index (AI) for ADCT-402 Administered Weekly (QW)
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort. AI is the ratio of AUC 0-24 after multiple doses versus a single dose. It is the increase in drug plasma concentration after multiple dosing until a steady state is reached.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Weekly (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 1.13 ratio | Standard Deviation 0.041 |
| 15 μg/kg Q3W | Accumulation Index (AI) for ADCT-402 Administered Weekly (QW) | Total Ab (ADCT-402) : Cycle 1 Week 2 | 2.52 ratio | Standard Deviation 1.92 |
Secondary
Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W)
Apparent clearance for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.650 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 0.495 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.422 L/day | — |
| 30 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 31.3 L/day | Standard Deviation 40 |
| 30 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 14.0 L/day | Standard Deviation 14.3 |
| 30 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 69.3 L/day | Standard Deviation 92.3 |
| 30 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 16.4 L/day | Standard Deviation 19.9 |
| 60 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 146 L/day | — |
| 60 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 86.4 L/day | Standard Deviation 34.6 |
| 60 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 55.5 L/day | — |
| 90 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.831 L/day | — |
| 90 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 80.8 L/day | Standard Deviation 106 |
| 90 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 3.98 L/day | — |
| 90 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 9.63 L/day | Standard Deviation 12.5 |
| 120 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 31.1 L/day | Standard Deviation 37 |
| 120 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 84.3 L/day | Standard Deviation 102 |
| 120 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 838 L/day | — |
| 120 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 10.3 L/day | Standard Deviation 16.7 |
| 150 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1.37 L/day | Standard Deviation 0.656 |
| 150 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1.57 L/day | Standard Deviation 0.726 |
| 150 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 18.9 L/day | Standard Deviation 21.8 |
| 150 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 27.4 L/day | Standard Deviation 12.4 |
Secondary
Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW)
Apparent clearance for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 5.77 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 14.0 L/day | Standard Deviation 18 |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 3 | 1.01 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 5.23 L/day | Standard Deviation 5.16 |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 3 | 2.03 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 1 | 8.46 L/day | — |
| 15 μg/kg Q3W | Apparent Clearance at Steady State for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 3 | 1.21 L/day | — |
Secondary
Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W)
T1/2 for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 5.23 days | — |
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 2.91 days | — |
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 4.42 days | — |
| 30 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1.28 days | Standard Deviation 1.66 |
| 30 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 1.87 days | Standard Deviation 0.287 |
| 30 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 4.31 days | Standard Deviation 6.62 |
| 30 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 15.0 days | Standard Deviation 6.88 |
| 60 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0342 days | — |
| 60 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 0.282 days | — |
| 60 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0538 days | — |
| 90 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 5.59 days | — |
| 90 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.355 days | Standard Deviation 0.501 |
| 90 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.784 days | — |
| 90 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 4.96 days | — |
| 120 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 7.55 days | Standard Deviation 10.3 |
| 120 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.156 days | Standard Deviation 0.164 |
| 120 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.508 days | — |
| 120 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 14.5 days | Standard Deviation 16.4 |
| 150 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 4.67 days | Standard Deviation 1.68 |
| 150 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 3.99 days | Standard Deviation 0.723 |
| 150 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.275 days | Standard Deviation 0.306 |
| 150 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.713 days | Standard Deviation 0.596 |
Secondary
Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every Week (QW)
T1/2 for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 2.29 days | — |
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 2.26 days | Standard Deviation 0.288 |
| 15 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (T1/2) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 9.39 days | Standard Deviation 9.77 |
Secondary
Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W)
Vd beta for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 4.91 liters | — |
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 2.08 liters | — |
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 2.69 liters | — |
| 30 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 9.77 liters | Standard Deviation 1.09 |
| 30 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 40.7 liters | Standard Deviation 44.3 |
| 30 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 24.0 liters | Standard Deviation 18.1 |
| 30 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 145 liters | Standard Deviation 190 |
| 60 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 7.22 liters | — |
| 60 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 45.1 liters | — |
| 60 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 4.31 liters | — |
| 90 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 6.71 liters | — |
| 90 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 10.5 liters | Standard Deviation 12.6 |
| 90 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 4.50 liters | — |
| 90 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 5.61 liters | — |
| 120 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 8.33 liters | Standard Deviation 5.43 |
| 120 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 6.89 liters | Standard Deviation 3.13 |
| 120 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 614 liters | — |
| 120 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 11.4 liters | Standard Deviation 0.101 |
| 150 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 9.14 liters | Standard Deviation 5.96 |
| 150 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 9.45 liters | Standard Deviation 5.27 |
| 150 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 2.68 liters | Standard Deviation 0.309 |
| 150 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 34.2 liters | Standard Deviation 35.5 |
Secondary
Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every Week (QW)
Vd beta for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 19.1 liters | — |
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 49.5 liters | Standard Deviation 64.6 |
| 15 μg/kg Q3W | Apparent Volume of Distribution (Vd Beta) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 107 liters | Standard Deviation 144 |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W)
AUC∞ for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 1378 day*ug/L | — |
| 30 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 395 day*ug/L | Standard Deviation 371 |
| 30 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 535 day*ug/L | Standard Deviation 668 |
| 60 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 94.1 day*ug/L | — |
| 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 677 day*ug/L | Standard Deviation 1091 |
| 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1634 day*ug/L | — |
| 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 282 day*ug/L | Standard Deviation 324 |
| 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1140 day*ug/L | Standard Deviation 1283 |
| 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 486 day*ug/L | Standard Deviation 259 |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Weekly (QW)
AUC∞ for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUC∞) for ADCT-402 Administered Weekly (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 545 day*ug/L |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W)
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 2500 day*ug/L | — |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1810 day*ug/L | — |
| 30 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 985 day*ug/L | Standard Deviation 1606 |
| 30 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1607 day*ug/L | Standard Deviation 2330 |
| 60 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 53.3 day*ug/L | Standard Deviation 9.99 |
| 60 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 41.2 day*ug/L | — |
| 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 3595 day*ug/L | Standard Deviation 4876 |
| 90 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 7820 day*ug/L | — |
| 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 8282 day*ug/L | Standard Deviation 14386 |
| 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 10198 day*ug/L | Standard Deviation 15433 |
| 120 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.104 day*ug/L | — |
| 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 7444 day*ug/L | Standard Deviation 831 |
| 150 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 10112 day*ug/L | Standard Deviation 1753 |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | — day*ug/L | — |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW)
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 1293 day*ug/L | Standard Deviation 1640 |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 3 | 3542 day*ug/L | — |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 1402 day*ug/L | Standard Deviation 1314 |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 3 | 2066 day*ug/L | — |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 1 | 449 day*ug/L | — |
| 15 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 3 | 3463 day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 1 Week 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 1 Week 2 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 1 Week 3 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 2 Week 2 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 2 Week 3 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | SG3199 : Cycle 2 Week 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 3 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 2 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 1 | — day*ug/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUC0-tau) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 2 | — day*ug/L | — |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 Administered Every 3 Weeks (Q3W)
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1012 day*ug/L | Standard Deviation 1301 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 610 day*ug/L | Standard Deviation 1190 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1596 day*ug/L | — |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 337 day*ug/L | Standard Deviation 651 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 127 day*ug/L | Standard Deviation 229 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.00522 day*ug/L | — |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1140 day*ug/L | Standard Deviation 2096 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.00355 day*ug/L | Standard Deviation 0.00147 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 735 day*ug/L | Standard Deviation 1400 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 408 day*ug/L | Standard Deviation 623 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 40.2 day*ug/L | Standard Deviation 0.0244 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 50.6 day*ug/L | Standard Deviation 9.08 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 43.0 day*ug/L | Standard Deviation 37.3 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0129 day*ug/L | — |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 59.9 day*ug/L | Standard Deviation 43.5 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 558 day*ug/L | Standard Deviation 899 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 3370 day*ug/L | Standard Deviation 4562 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.00830 day*ug/L | — |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.00930 day*ug/L | Standard Deviation 0.00675 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 671 day*ug/L | Standard Deviation 1083 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 3671 day*ug/L | Standard Deviation 5062 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 5718 day*ug/L | Standard Deviation 9648 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 3907 day*ug/L | Standard Deviation 8159 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 8744 day*ug/L | Standard Deviation 17745 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 13519 day*ug/L | Standard Deviation 22799 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0194 day*ug/L | Standard Deviation 0.0231 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0433 day*ug/L | Standard Deviation 0.0316 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0338 day*ug/L | Standard Deviation 0.015 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1091 day*ug/L | Standard Deviation 673 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 7553 day*ug/L | Standard Deviation 727 |
| 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 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 688 day*ug/L | Standard Deviation 570 |
| 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 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 10493 day*ug/L | Standard Deviation 2021 |
| 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 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.00927 day*ug/L | Standard Deviation 0.00881 |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-402 Administered Every Week (QW)
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 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 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 518 day*ug/L | — |
| 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 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 1063 day*ug/L | Standard Deviation 1334 |
| 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 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 1 | 1548 day*ug/L | — |
| 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 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 2 | 2631 day*ug/L | — |
| 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 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 3 | 3918 day*ug/L | — |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 1 | 464 day*ug/L | Standard Deviation 290 |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 821 day*ug/L | Standard Deviation 886 |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 3 | 1286 day*ug/L | Standard Deviation 1158 |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 1 | 1157 day*ug/L | Standard Deviation 962 |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 2 | 9.08 day*ug/L | Standard Deviation 9.78 |
| 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 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 3 | 3927 day*ug/L | — |
Secondary
Duration of Response
Duration of response is defined among responders (complete response \[CR\], complete response with incomplete blood count recovery \[Cri\], 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. Disease progression is defined as: * For participants with CR or CRi, the first date of reappearance of blast cells in bone marrow and/or peripheral blood to a level ≥5%, or development of extramedullary disease. * For participants with PR, the first date of an increase in blast cells in bone marrow and/or peripheral blood such that the patient does not continue to meet the criteria for PR.
Time frame: From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W)
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1251 µg/L | Standard Deviation 1724 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 205 µg/L | Standard Deviation 162 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 2150 µg/L | — |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 178 µg/L | Standard Deviation 128 |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 258 µg/L | Standard Deviation 162 |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0459 µg/L | — |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 366 µg/L | Standard Deviation 251 |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0428 µg/L | Standard Deviation 0.0000707 |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 339 µg/L | Standard Deviation 276 |
| 30 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 317 µg/L | Standard Deviation 194 |
| 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 689 µg/L | Standard Deviation 382 |
| 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 661 µg/L | Standard Deviation 412 |
| 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 449 µg/L | Standard Deviation 282 |
| 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0697 µg/L | — |
| 60 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 717 µg/L | Standard Deviation 429 |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1049 µg/L | Standard Deviation 892 |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1813 µg/L | Standard Deviation 1650 |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0551 µg/L | — |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0617 µg/L | Standard Deviation 0.0238 |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 1058 µg/L | Standard Deviation 893 |
| 90 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 1845 µg/L | Standard Deviation 1676 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 1722 µg/L | Standard Deviation 785 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 1291 µg/L | Standard Deviation 1020 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 1515 µg/L | Standard Deviation 1001 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 2125 µg/L | Standard Deviation 944 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0810 µg/L | Standard Deviation 0.0288 |
| 120 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.108 µg/L | Standard Deviation 0.0239 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0907 µg/L | Standard Deviation 0.05 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 2761 µg/L | Standard Deviation 1718 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 2 | 3033 µg/L | Standard Deviation 1458 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 2145 µg/L | Standard Deviation 1054 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 4338 µg/L | Standard Deviation 2460 |
| 150 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0550 µg/L | Standard Deviation 0.0277 |
Secondary
Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW)
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 777 µg/L | — |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 788 µg/L | Standard Deviation 456 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 1 | 444 µg/L | — |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 2 | 757 µg/L | — |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 3 | 773 µg/L | — |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 1 | 363 µg/L | Standard Deviation 390 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 544 µg/L | Standard Deviation 492 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 3 | 293 µg/L | Standard Deviation 313 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 1 | 300 µg/L | Standard Deviation 294 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 2 | 480 µg/L | Standard Deviation 414 |
| 15 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 3 | 730 µg/L | — |
Secondary
Mean Residence Time for ADCT-402
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
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.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA pre-dose | 1 Participants |
| 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA post-dose | 0 Participants |
| 15 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (ADA) Against ADCT-402 | Confirmed positive ADA at any time | 1 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the number of participants with a best overall response of complete response (CR), complete response with incomplete blood count recovery (Cri) or partial response (PR) at the time each participant discontinues treatment with ADCT-402. CR is defined as achieving each of the following: * Bone marrow differential showing ≤5% blast cells. * Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Absence of extramedullary disease. * Participant is independent of red blood cell transfusions. Cri is defined as achieving all CR criteria except that values for ANC may be \<1.0 x 10\^9/L and/or values for platelets may be \<100 x 10\^9/L. PR is defined as achieving each of the following: * ANC ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level \>5% and ≤25%, or bone marrow differential showing \<5% blast cells.
Time frame: From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Overall Survival
Overall survival is defined as the time from the first dose of study drug treatment until the date of death due to any cause.
Time frame: From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Progression-free Survival
Progression-free survival is 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: From 6 days prior to Day 1 of Cycle 3 and 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Terminal Elimination Phase Rate Constant for ADCT-402
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W)
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the Q3W cohorts.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0600 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0600 days | Standard Deviation 0.0216 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0600 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0525 days | Standard Deviation 0.00957 |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0671 days | Standard Deviation 0.0547 |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0600 days | — |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0700 days | Standard Deviation 0.0678 |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0600 days | Standard Deviation 0.0283 |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0475 days | Standard Deviation 0.025 |
| 30 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0729 days | Standard Deviation 0.0547 |
| 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0300 days | Standard Deviation 0.0141 |
| 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0300 days | Standard Deviation 0.0141 |
| 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0433 days | Standard Deviation 0.00577 |
| 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0600 days | — |
| 60 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0450 days | Standard Deviation 0.00707 |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0433 days | Standard Deviation 0.00577 |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0500 days | Standard Deviation 0.0424 |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0400 days | — |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.125 days | Standard Deviation 0.0636 |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0567 days | Standard Deviation 0.0208 |
| 90 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0500 days | Standard Deviation 0.0424 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0450 days | Standard Deviation 0.00577 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0460 days | Standard Deviation 0.00548 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0500 days | Standard Deviation 0.0212 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0600 days | Standard Deviation 0.0141 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.0867 days | Standard Deviation 0.00577 |
| 120 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0867 days | Standard Deviation 0.00577 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 1 | 0.395 days | Standard Deviation 0.777 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 1 | 0.0517 days | Standard Deviation 0.00983 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab: Cycle 2 | 0.0525 days | Standard Deviation 0.025 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | PBD-Conjugated Ab : Cycle 1 | 0.0517 days | Standard Deviation 0.00983 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | Total Ab (ADCT-402) : Cycle 2 | 0.0625 days | Standard Deviation 0.0263 |
| 150 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every 3 Weeks (Q3W) | SG3199 : Cycle 2 | 0.0600 days | Standard Deviation 0.0283 |
Secondary
Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW)
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for the QW cohort.
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were non-measurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 1 | 0.0500 days | Standard Deviation 0.01 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 1 | 0.0500 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 1 Week 2 | 0.0400 days | Standard Deviation 0.0141 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 1 | 0.0400 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 2 | 0.0400 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | PBD-Conjugated Ab : Cycle 2 Week 3 | 0.0400 days | — |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 2 | 0.697 days | Standard Deviation 1.14 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 1 Week 3 | 0.110 days | Standard Deviation 0.0849 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 1 | 0.0400 days | Standard Deviation 0 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 2 | 0.0300 days | Standard Deviation 0.0141 |
| 15 μg/kg Q3W | Time to Reach the Maximum Serum Concentration (Tmax) for ADCT-402 Administered Every Week (QW) | Total Ab (ADCT-402): Cycle 2 Week 3 | 0.0400 days | — |
Secondary
Volume of Distribution at Steady State for ADCT-402
Time frame: Day 1 (before infusion, end of infusion, and 1, 3 and 6 hours after infusion) and Days 2, 3, 5, 8 and 15 for Cycles 1 and 2
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.