Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Conditions
Keywords
Camidanlumab tesirine
Brief summary
This study evaluates ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). Participants will participate in a dose-escalation phase (Part 1) and receive ADCT-301 either weekly or once every 3 weeks. In Part 2 of the study, participants will receive a recommended dose of ADCT-301 as determined by a Dose Escalation Steering Committee.
Detailed description
This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and pharmacokinetics of ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells, covalently cross links deoxyribonucleic acid (DNA) preventing replication. The study will be conducted in 2 parts: In Part 1 (dose escalation) participants will either be on weekly administration or every 3-week administration. Participants on weekly administration will receive an infusion of ADCT-301 on Days 1, 8, and 15 of each 3 week treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-301 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined. In Part 2 (expansion), participants will be assigned to receive a recommended dose and/or schedule of ADCT-301 as determined by a Dose Escalation Steering Committee. For each participant, the study will include a screening period (up to 28 days), a treatment period, and a follow-up period to assess disease progression and survival for up to 12 months after the last dose of study drug. The total study duration will be dependent on overall participant tolerability to the study drug and response to treatment. It is anticipated that the entire study (Parts 1 and 2) will enroll a maximum of 80 participants and could last approximately 3 years from first participant treated to last participant completed.
Interventions
DRUGADCT-301
Intravenous infusion
Sponsors
ADC Therapeutics S.A.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory CD25-positive AML \[per World Health Organization (WHO)\]. * Relapsed or refractory CD25-positive ALL \[per World Health Organization (WHO)\]. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Creatinine ≤1.5mg/dL. * Serum/plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤5 times ULN if there is liver or bone involvement. * Total serum/plasma bilirubin ≤1.5 times the upper limit of normal. * Women of childbearing potential must have a negative urine or serum beta-human chorionic gonadotropin pregnancy test within 7 days prior to Day 1. * Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception. * White Blood Cell Count value of \<15,000 cells/μL prior to Cycle 1 Day 1.
Exclusion criteria
* Participants who have an option for any treatment with proven clinical benefit for CD25-positive AML or CD25-positive ALL at current state of disease. * Known active central nervous system (CNS) leukemia, defined as morphologic evidence of leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal treatment for active disease within 28 days prior to Screening, or symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days prior to Screening. * Active graft versus host disease. * Autologous or allogenic transplant within the 60 days prior to Screening. * Known history of immunogenicity or hypersensitivity to a CD25 antibody. * Known history of positive serum human anti-drug antibodies (ADA), or known allergy to any component of ADCT-301. * Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral therapy. * History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome. * Pregnant or breastfeeding women. * Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure \>115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, myocardial infarction within 6 months prior to Screening, or uncontrolled atrial or ventricular cardiac arrhythmias. * Use of any other experimental medication(s) within 14 days or 5 half-lives but in no case \< 14 days prior to the start of the study treatment on Cycle 1, Day 1. * Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted therapies within 14 days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except if approved by the Sponsor. * Failure to recover (to CTCAE Version 4.0 Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening. * Isolated extramedullary relapse (i.e., testicular, CNS). * Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening (unless secondary to pacemaker or bundle branch block). * Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy. * Any other significant medical illness, abnormality, or condition.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | Day 1 to Day 21 (Cycle 1) | A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome. * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration. * Peripheral sensory or motor neuropathy ≥ Grade 2. |
| Recommended Dose of ADCT-301 for Part 2 | Day 1 to Day 21 (Cycle 1) | The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study. |
| Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | Day 1 to a maximum of 24 weeks (+ 30 days) | A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug. |
| Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | Day 1 to a maximum of 24 weeks (+ 30 days) | An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days) | DOR is defined among responders (complete response \[CR\], CR with incomplete blood count recover \[CRi\], or partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. CR: * Bone marrow differential showing ≤5% blast cells. * Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Absence of extramedullary disease. * Participant is independent of red blood cell transfusions. CRi is defined as achieving all CR criteria except that values for ANC may be \<1.0 x 10\^9/L and/or values for platelets may be \<100 x 10\^9/L. PR: * ANC ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level \>5% and ≤25%, or bone marrow differential showing \<5% blast cells. |
| Overall Response Rate (ORR) | Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days) | ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders. |
| Overall Survival (OS) | Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days) | OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. |
| Number of Participants With Progression Free Survival (PFS) | Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days) | PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. |
| Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts. |
| Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1. |
| Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1. |
| Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days) | CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. |
| Clearance (CL) for ADCT-301 for the QW Dosing Schedule | Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days) | CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. |
| Number of Participants With Anti-drug Antibody Response (Against ADCT-301) | Day 1 to the end of Cycle 2 (6 weeks) | Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 11 sites in the United States between 01 February 2016 and 29 August 2018.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 3 μg/kg Q3W Participants received 3 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 4 |
| Cohort 2: 6 μg/kg Q3W Participants received 6 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 3: 12 μg/kg Q3W Participants received 12 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 4: 22 μg/kg Q3W Participants received 22 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 5: 32 μg/kg Q3W Participants received 32 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 6: 52 μg/kg Q3W Participants received 52 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 7: 72 μg/kg Q3W Participants received 72 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 3 |
| Cohort 8: 92 μg/kg Q3W Participants received 92 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Day 1 of each 3-week (21-day) cycle (Q3W). | 4 |
| Cohort 9: 30 μg/kg QW Participants received 30 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly \[QW\]) of each 3-week (21 day) cycle. | 6 |
| Cohort 10: 37.5 μg/kg QW Participants received 37.5 μg/kg ADCT-301 formulation, intravenous infusion for 1 hour, on Days 1, 8 and 15 (once weekly \[QW\]) of each 3-week (21 day) cycle. | 3 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 3 | 3 | 3 | 2 | 2 | 2 | 1 | 5 | 2 |
| Overall Study | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Started Another Treatment | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2: 6 μg/kg Q3W | Cohort 3: 12 μg/kg Q3W | Cohort 4: 22 μg/kg Q3W | Cohort 5: 32 μg/kg Q3W | Cohort 6: 52 μg/kg Q3W | Cohort 1: 3 μg/kg Q3W | Cohort 7: 72 μg/kg Q3W | Cohort 8: 92 μg/kg Q3W | Cohort 9: 30 μg/kg QW | Cohort 10: 37.5 μg/kg QW | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 12 Participants |
| Age, Continuous | 72.3 years STANDARD_DEVIATION 4.73 | 51.0 years STANDARD_DEVIATION 17.78 | 51.7 years STANDARD_DEVIATION 26.27 | 69.3 years STANDARD_DEVIATION 2.89 | 67.0 years STANDARD_DEVIATION 13 | 66.8 years STANDARD_DEVIATION 11.09 | 75.7 years STANDARD_DEVIATION 5.69 | 56.5 years STANDARD_DEVIATION 18.43 | 71.0 years STANDARD_DEVIATION 10.77 | 63.3 years STANDARD_DEVIATION 10.02 | 64.9 years STANDARD_DEVIATION 14.21 |
| Body Mass Index (BMI) | 31.09 kg/m^2 STANDARD_DEVIATION 4.209 | 21.94 kg/m^2 STANDARD_DEVIATION 2.469 | 24.89 kg/m^2 STANDARD_DEVIATION 3.002 | 33.86 kg/m^2 STANDARD_DEVIATION 7.003 | 25.98 kg/m^2 STANDARD_DEVIATION 1.259 | 29.37 kg/m^2 STANDARD_DEVIATION 3.1 | 25.52 kg/m^2 STANDARD_DEVIATION 6.243 | 27.47 kg/m^2 STANDARD_DEVIATION 3.759 | 26.03 kg/m^2 STANDARD_DEVIATION 3.607 | 23.94 kg/m^2 STANDARD_DEVIATION 0.934 | 26.94 kg/m^2 STANDARD_DEVIATION 4.656 |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 2 Participants | 27 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 2 | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 6 Participants | 3 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 179.27 cm STANDARD_DEVIATION 15.255 | 183.20 cm STANDARD_DEVIATION 9.354 | 170.00 cm STANDARD_DEVIATION 4.359 | 176.33 cm STANDARD_DEVIATION 4.856 | 165.50 cm STANDARD_DEVIATION 18.007 | 169.40 cm STANDARD_DEVIATION 10.641 | 168.57 cm STANDARD_DEVIATION 6.562 | 169.38 cm STANDARD_DEVIATION 11.762 | 169.52 cm STANDARD_DEVIATION 12.478 | 177.22 cm STANDARD_DEVIATION 3.586 | 172.44 cm STANDARD_DEVIATION 10.774 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 33 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants | 4 participants | 3 participants | 4 participants | 6 participants | 3 participants | 35 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 25 Participants |
| Weight | 99.30 kg STANDARD_DEVIATION 12.644 | 73.50 kg STANDARD_DEVIATION 7.988 | 72.20 kg STANDARD_DEVIATION 11.722 | 105.67 kg STANDARD_DEVIATION 24.509 | 71.63 kg STANDARD_DEVIATION 15.053 | 94.98 kg STANDARD_DEVIATION 24.758 | 71.67 kg STANDARD_DEVIATION 11.395 | 79.45 kg STANDARD_DEVIATION 17.436 | 74.10 kg STANDARD_DEVIATION 5.686 | 75.23 kg STANDARD_DEVIATION 5.2 | 81.43 kg STANDARD_DEVIATION 17.597 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 2 / 3 | 2 / 3 | 2 / 3 | 1 / 4 | 5 / 6 | 2 / 3 |
| other Total, other adverse events | 4 / 4 | 2 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 2 / 4 | 1 / 3 | 2 / 3 | 3 / 3 | 1 / 3 | 2 / 3 | 2 / 3 | 2 / 4 | 5 / 6 | 3 / 3 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.
Time frame: Day 1 to a maximum of 24 weeks (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Cohort 2: 6 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| Cohort 3: 12 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 4: 22 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 5: 32 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 6: 52 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 7: 72 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Cohort 8: 92 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 4 Participants |
| Cohort 9: 30 μg/kg QW | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 6 Participants |
| Cohort 10: 37.5 μg/kg QW | Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
Primary
Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)
An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.
Time frame: Day 1 to a maximum of 24 weeks (+ 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Cohort 2: 6 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Cohort 3: 12 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Cohort 4: 22 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 3 Participants |
| Cohort 5: 32 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 1 Participants |
| Cohort 6: 52 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Cohort 7: 72 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Cohort 8: 92 μg/kg Q3W | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 2 Participants |
| Cohort 9: 30 μg/kg QW | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 5 Participants |
| Cohort 10: 37.5 μg/kg QW | Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE) | 3 Participants |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)
A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome. * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration. * Peripheral sensory or motor neuropathy ≥ Grade 2.
Time frame: Day 1 to Day 21 (Cycle 1)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 2: 6 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 3: 12 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 4: 22 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 5: 32 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 6: 52 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 7: 72 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 8: 92 μg/kg Q3W | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
| Cohort 9: 30 μg/kg QW | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 1 Participants |
| Cohort 10: 37.5 μg/kg QW | Number of Participants Who Experienced Dose-Limiting Toxicities (DLT) | 0 Participants |
Primary
Recommended Dose of ADCT-301 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 Day 21 (Cycle 1)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
Secondary
Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 21 days for Cycle 2 divided by AUC from 0 to 21 days for Cycle 1.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0.416 |
| Cohort 5: 32 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0.373 |
| Cohort 6: 52 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.00 ratio | — |
| Cohort 6: 52 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0 |
| Cohort 7: 72 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0.0434 |
| Cohort 7: 72 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0.113 |
| Cohort 8: 92 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.00 ratio | Geometric Coefficient of Variation 0.000222 |
| Cohort 8: 92 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.00 ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | — ratio | — |
Secondary
Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule
AI for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort. AI is the ratio of area under the serum concentration-time curve (AUC) from 0 to 7 days divided by AUC from 7 to 14 days for Cycle 1.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 1.13 ratio | Geometric Coefficient of Variation 9.77 |
| Cohort 1: 3 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 1.12 ratio | Geometric Coefficient of Variation 14.3 |
| Cohort 2: 6 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 1.00 ratio | — |
| Cohort 2: 6 μg/kg Q3W | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 1.00 ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | — ratio | — |
| Unknown | Accumulation Index (AI) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — ratio | — |
Secondary
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.995 days | Geometric Coefficient of Variation 45.8 |
| Cohort 5: 32 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.80 days | Geometric Coefficient of Variation 67.7 |
| Cohort 5: 32 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.96 days | Geometric Coefficient of Variation 55.8 |
| Cohort 6: 52 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 2.28 days | — |
| Cohort 6: 52 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.379 days | Geometric Coefficient of Variation 63.9 |
| Cohort 7: 72 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 2.28 days | — |
| Cohort 7: 72 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.36 days | Geometric Coefficient of Variation 56 |
| Cohort 7: 72 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 2.18 days | — |
| Cohort 7: 72 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1.57 days | Geometric Coefficient of Variation 55.5 |
| Cohort 8: 92 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.587 days | — |
| Cohort 8: 92 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.446 days | Geometric Coefficient of Variation 45.6 |
| Cohort 8: 92 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1.02 days | — |
| Cohort 8: 92 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.451 days | Geometric Coefficient of Variation 111 |
Secondary
Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule
Thalf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 0.719 days |
| Unknown | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — days |
| Unknown | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | — days |
| Unknown | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | — days |
| Unknown | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — days |
| Unknown | Apparent Terminal Phase Elimination Half-life (Thalf) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — days |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 667 day*μg/L | Geometric Coefficient of Variation 56.3 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1631 day*μg/L | — |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 2846 day*μg/L | — |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 3434 day*μg/L | — |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 440 day*μg/L | Geometric Coefficient of Variation 139 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1019 day*μg/L | — |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule
AUCinf for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 366 day*μg/L |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — day*μg/L |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | — day*μg/L |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | — day*μg/L |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — day*μg/L |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — day*μg/L |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1700 day*μg/L | Geometric Coefficient of Variation 89.6 |
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1061 day*μg/L | Geometric Coefficient of Variation 72.3 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 60.2 day*μg/L | — |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 186 day*μg/L | Geometric Coefficient of Variation 240 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1248 day*μg/L | Geometric Coefficient of Variation 114 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1751 day*μg/L | Geometric Coefficient of Variation 146 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 622 day*μg/L | Geometric Coefficient of Variation 167 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 826 day*μg/L | Geometric Coefficient of Variation 151 |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | — day*μg/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | — day*μg/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | — day*μg/L | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | — day*μg/L | — |
Secondary
Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule
AUCtau for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — |
| Unknown | Area Under the Serum Concentration-time Curve From Time 0 to the End of the Dosing Interval (AUCtau) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 36.3 day*μg/L | Geometric Coefficient of Variation 245 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 19.1 day*μg/L | Geometric Coefficient of Variation 7.42 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 22.6 day*μg/L | Geometric Coefficient of Variation 23.9 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 19.0 day*μg/L | Geometric Coefficient of Variation 681 |
| Cohort 3: 12 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 109 day*μg/L | — |
| Cohort 3: 12 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 132 day*μg/L | — |
| Cohort 4: 22 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 46.4 day*μg/L | Geometric Coefficient of Variation 353 |
| Cohort 4: 22 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 34.9 day*μg/L | Geometric Coefficient of Variation 363 |
| Cohort 4: 22 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 30.4 day*μg/L | — |
| Cohort 4: 22 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 22.6 day*μg/L | Geometric Coefficient of Variation 77.7 |
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 231 day*μg/L | Geometric Coefficient of Variation 1225 |
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 590 day*μg/L | Geometric Coefficient of Variation 40.6 |
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 317 day*μg/L | Geometric Coefficient of Variation 43.3 |
| Cohort 5: 32 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 348 day*μg/L | Geometric Coefficient of Variation 1389 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.00600 day*μg/L | Geometric Coefficient of Variation 110 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 114 day*μg/L | Geometric Coefficient of Variation 332 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.00500 day*μg/L | — |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1144 day*μg/L | Geometric Coefficient of Variation 66.7 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 897 day*μg/L | Geometric Coefficient of Variation 67.5 |
| Cohort 6: 52 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 127 day*μg/L | Geometric Coefficient of Variation 452 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 1198 day*μg/L | Geometric Coefficient of Variation 82.1 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1577 day*μg/L | Geometric Coefficient of Variation 69.6 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1427 day*μg/L | Geometric Coefficient of Variation 180 |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.0120 day*μg/L | — |
| Cohort 7: 72 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1063 day*μg/L | Geometric Coefficient of Variation 135 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 436 day*μg/L | Geometric Coefficient of Variation 178 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.0500 day*μg/L | Geometric Coefficient of Variation 81.2 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 360 day*μg/L | Geometric Coefficient of Variation 180 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.01540 day*μg/L | — |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 394 day*μg/L | Geometric Coefficient of Variation 174 |
| Cohort 8: 92 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 381 day*μg/L | Geometric Coefficient of Variation 126 |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule
AUClast for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 331 day*μg/L | Geometric Coefficient of Variation 114 |
| Cohort 1: 3 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 378 day*μg/L | Geometric Coefficient of Variation 103 |
| Cohort 1: 3 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 476 day*μg/L | Geometric Coefficient of Variation 116 |
| Cohort 1: 3 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 584 day*μg/L | Geometric Coefficient of Variation 86.8 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 3099 day*μg/L | — |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 113 day*μg/L | Geometric Coefficient of Variation 86.8 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 152 day*μg/L | Geometric Coefficient of Variation 103 |
| Cohort 2: 6 μg/kg Q3W | Area Under the Serum Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 2319 day*μg/L | — |
Secondary
Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 4.22 L/day | Geometric Coefficient of Variation 86.9 |
| Cohort 5: 32 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 2.68 L/day | Geometric Coefficient of Variation 40.6 |
| Cohort 5: 32 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 2.12 L/day | Geometric Coefficient of Variation 54.5 |
| Cohort 6: 52 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 2.21 L/day | — |
| Cohort 6: 52 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 14.5 L/day | Geometric Coefficient of Variation 423 |
| Cohort 7: 72 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 1.67 L/day | — |
| Cohort 7: 72 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 3.28 L/day | Geometric Coefficient of Variation 84.1 |
| Cohort 7: 72 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1.75 L/day | — |
| Cohort 7: 72 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 2.96 L/day | Geometric Coefficient of Variation 109 |
| Cohort 8: 92 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 5.36 L/day | — |
| Cohort 8: 92 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 12.5 L/day | Geometric Coefficient of Variation 237 |
| Cohort 8: 92 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 8.20 L/day | Geometric Coefficient of Variation 163 |
| Cohort 8: 92 μg/kg Q3W | Clearance (CL) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 12.6 L/day | Geometric Coefficient of Variation 151 |
Secondary
Clearance (CL) for ADCT-301 for the QW Dosing Schedule
CL for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 6.59 L/day |
| Unknown | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — L/day |
| Unknown | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | — L/day |
| Unknown | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | — L/day |
| Unknown | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — L/day |
| Unknown | Clearance (CL) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — L/day |
Secondary
Duration of Response (DOR)
DOR is defined among responders (complete response \[CR\], CR with incomplete blood count recover \[CRi\], or partial response \[PR\]) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders. CR: * Bone marrow differential showing ≤5% blast cells. * Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Absence of extramedullary disease. * Participant is independent of red blood cell transfusions. CRi is defined as achieving all CR criteria except that values for ANC may be \<1.0 x 10\^9/L and/or values for platelets may be \<100 x 10\^9/L. PR: * ANC ≥1.0 x 10\^9/L and platelet count ≥100 x 10\^9/L. * Bone marrow differential showing a ≥50% decrease from baseline in the percentage of bone marrow blast cells to a level \>5% and ≤25%, or bone marrow differential showing \<5% blast cells.
Time frame: Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
Secondary
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohorts.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 278 μg/L | Geometric Coefficient of Variation 355 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 79.2 μg/L | Geometric Coefficient of Variation 0.268 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 91.4 μg/L | Geometric Coefficient of Variation 17 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 181 μg/L | Geometric Coefficient of Variation 348 |
| Cohort 3: 12 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 165 μg/L | — |
| Cohort 3: 12 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 177 μg/L | — |
| Cohort 4: 22 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 233 μg/L | Geometric Coefficient of Variation 93.8 |
| Cohort 4: 22 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 186 μg/L | Geometric Coefficient of Variation 117 |
| Cohort 4: 22 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 589 μg/L | — |
| Cohort 4: 22 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 272 μg/L | Geometric Coefficient of Variation 236 |
| Cohort 5: 32 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 405 μg/L | Geometric Coefficient of Variation 383 |
| Cohort 5: 32 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 715 μg/L | Geometric Coefficient of Variation 139 |
| Cohort 5: 32 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 514 μg/L | Geometric Coefficient of Variation 127 |
| Cohort 5: 32 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 517 μg/L | Geometric Coefficient of Variation 330 |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.0140 μg/L | Geometric Coefficient of Variation 29.7 |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 284 μg/L | Geometric Coefficient of Variation 102 |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.0210 μg/L | — |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 960 μg/L | Geometric Coefficient of Variation 82.5 |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 920 μg/L | Geometric Coefficient of Variation 71.2 |
| Cohort 6: 52 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 333 μg/L | Geometric Coefficient of Variation 121 |
| Cohort 7: 72 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 877 μg/L | Geometric Coefficient of Variation 35.4 |
| Cohort 7: 72 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1013 μg/L | Geometric Coefficient of Variation 34.4 |
| Cohort 7: 72 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 1406 μg/L | Geometric Coefficient of Variation 199 |
| Cohort 7: 72 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.0140 μg/L | — |
| Cohort 7: 72 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 1182 μg/L | Geometric Coefficient of Variation 167 |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 910 μg/L | Geometric Coefficient of Variation 41 |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.0280 μg/L | Geometric Coefficient of Variation 54.3 |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 710 μg/L | Geometric Coefficient of Variation 41.6 |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.0170 μg/L | — |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 1196 μg/L | Geometric Coefficient of Variation 69.3 |
| Cohort 8: 92 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 949 μg/L | Geometric Coefficient of Variation 63.8 |
Secondary
Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule
Cmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 377 μg/L | Geometric Coefficient of Variation 67 |
| Cohort 1: 3 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 350 μg/L | Geometric Coefficient of Variation 32.8 |
| Cohort 1: 3 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 435 μg/L | Geometric Coefficient of Variation 63.5 |
| Cohort 1: 3 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 416 μg/L | Geometric Coefficient of Variation 33.8 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 15100 μg/L | — |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 355 μg/L | Geometric Coefficient of Variation 39.4 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 504 μg/L | Geometric Coefficient of Variation 22.2 |
| Cohort 2: 6 μg/kg Q3W | Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 13200 μg/L | — |
Secondary
Mean Residence Time (MRT) for ADCT-301 for the Q3W Dosing Schedule
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Mean Residence Time (MRT) for ADCT-301 for the QW Dosing Schedule
MRT analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
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 (Against ADCT-301)
Blood serum samples were collected and analysed to determine the presence or absence of ADA. Results were pooled for Part 1 participants as specified in the protocol.
Time frame: Day 1 to the end of Cycle 2 (6 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Number of Participants With Anti-drug Antibody Response (Against ADCT-301) | 2 Participants |
Secondary
Number of Participants With Progression Free Survival (PFS)
PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Time frame: Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response of CR, CRi, or PR at the time each participant discontinues treatment with ADCT-301. A summary of antitumor activity was not conducted due to a limited number of responders.
Time frame: Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
Secondary
Overall Survival (OS)
OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause. A summary of antitumor activity was not conducted due to a limited number of responders.
Time frame: Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)
Population: The analysis was planned, but the data was not collected as study was terminated prematurely.
Secondary
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the Q3W Dosing Schedule
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Terminal Elimination Phase Rate Constant (λz) for ADCT-301 for the QW Dosing Schedule
λz analysis was planned for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: This analysis was planned, but data was not collected as the study was terminated prematurely.
Secondary
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.162 days | Geometric Coefficient of Variation 34.6 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.144 days | Geometric Coefficient of Variation 21.7 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.103 days | Geometric Coefficient of Variation 27.2 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.162 days | Geometric Coefficient of Variation 34.6 |
| Cohort 3: 12 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.0870 days | — |
| Cohort 3: 12 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.0870 days | — |
| Cohort 4: 22 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.0830 days | Geometric Coefficient of Variation 3.01 |
| Cohort 4: 22 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.0830 days | Geometric Coefficient of Variation 3.01 |
| Cohort 4: 22 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.0490 days | — |
| Cohort 4: 22 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.0490 days | — |
| Cohort 5: 32 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.0620 days | Geometric Coefficient of Variation 33.9 |
| Cohort 5: 32 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.101 days | Geometric Coefficient of Variation 11.7 |
| Cohort 5: 32 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.0850 days | Geometric Coefficient of Variation 23.4 |
| Cohort 5: 32 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.0770 days | Geometric Coefficient of Variation 17.1 |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.228 days | Geometric Coefficient of Variation 12.8 |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.0860 days | Geometric Coefficient of Variation 2.45 |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.310 days | — |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.0910 days | Geometric Coefficient of Variation 5 |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.0910 days | Geometric Coefficient of Variation 5 |
| Cohort 6: 52 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.123 days | Geometric Coefficient of Variation 50.2 |
| Cohort 7: 72 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.108 days | Geometric Coefficient of Variation 20.1 |
| Cohort 7: 72 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.119 days | Geometric Coefficient of Variation 31.2 |
| Cohort 7: 72 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.0840 days | Geometric Coefficient of Variation 63.1 |
| Cohort 7: 72 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.379 days | — |
| Cohort 7: 72 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.0840 days | Geometric Coefficient of Variation 63.1 |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 0.0760 days | Geometric Coefficient of Variation 59.1 |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 | 0.164 days | Geometric Coefficient of Variation 36.1 |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 0.0810 days | Geometric Coefficient of Variation 45.1 |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 2 | 0.309 days | — |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 0.108 days | Geometric Coefficient of Variation 20.1 |
| Cohort 8: 92 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 0.108 days | Geometric Coefficient of Variation 20.1 |
Secondary
Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule
Tmax for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 0.0680 days | Geometric Coefficient of Variation 19.9 |
| Cohort 1: 3 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 0.0370 days | Geometric Coefficient of Variation 50.4 |
| Cohort 1: 3 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 0.117 days | Geometric Coefficient of Variation 185 |
| Cohort 1: 3 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 0.0370 days | Geometric Coefficient of Variation 50.4 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | 0.0240 days | — |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | 0.119 days | Geometric Coefficient of Variation 173 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 0.0590 days | Geometric Coefficient of Variation 18.1 |
| Cohort 2: 6 μg/kg Q3W | Time to Reach the Maximum Observed Serum Concentration (Tmax) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | 0.0240 days | — |
Secondary
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for Q3W cohort.
Time frame: Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 5: 32 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 5.69 liters | Geometric Coefficient of Variation 28.9 |
| Cohort 5: 32 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 6.46 liters | Geometric Coefficient of Variation 13.9 |
| Cohort 5: 32 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 5.74 liters | Geometric Coefficient of Variation 2.99 |
| Cohort 6: 52 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 7.04 liters | — |
| Cohort 6: 52 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 7.58 liters | Geometric Coefficient of Variation 168 |
| Cohort 7: 72 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 4.27 liters | — |
| Cohort 7: 72 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 5.94 liters | Geometric Coefficient of Variation 25.7 |
| Cohort 7: 72 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 4.54 liters | — |
| Cohort 7: 72 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 6.22 liters | Geometric Coefficient of Variation 43.3 |
| Cohort 8: 92 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 1 | 3.88 liters | — |
| Cohort 8: 92 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 | 7.34 liters | Geometric Coefficient of Variation 120 |
| Cohort 8: 92 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 2 | 5.29 liters | — |
| Cohort 8: 92 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the Q3W Dosing Schedule | Total Ab of ADCT-301: Cycle 2 | 7.83 liters | Geometric Coefficient of Variation 37.1 |
Secondary
Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule
Vss for Pyrrolobenzodiazepine (PBD) conjugated antibody (Ab), total Ab and free warhead (SG3199) for QW cohort.
Time frame: Before infusion, end of infusion, 5, 24, 48, and 96 hours after infusion on days 1 and 8, and before and after infusion on Day 15 of Cycle 1 and 2 (1 cycle = 21 days)
Population: Only participants with evaluable pharmacokinetic results were included in the analysis. Where data is not presented, the pharmacokinetic profiles were nonmeasurable or short-lived in duration; therefore, no analysis could be performed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1: 3 μg/kg Q3W | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 1 | 6.07 liters |
| Unknown | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 1 | — liters |
| Unknown | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | PBD-conjugated Ab of ADCT-301: Cycle 1 Week 2 | — liters |
| Unknown | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | Total Ab of ADCT-301: Cycle 1 Week 2 | — liters |
| Unknown | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 1 | — liters |
| Unknown | Volume of Distribution at Steady-state (Vss) for ADCT-301 for the QW Dosing Schedule | SG3199 Free Warhead of ADCT-301: Cycle 1 Week 2 | — liters |