This multicenter, open-label, dose-escalating study will assess the safety, tolerability, and pharmacokinetics of DMOT4039A in participants with unresectable pancreatic or platinum-resistant ovarian cancer. Cohorts of participants will receive multiple ascending intravenous doses of DMOT4039A.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
DMOT4093A will be administered by intravenous infusion on either a Q3W or a Q1W dosing schedule, in 21-day cycles.
Unnamed facility
Phoenix, Arizona, United States
Unnamed facility
Aurora, Colorado, United States
Unnamed facility
Jacksonville, Florida, United States
Unnamed facility
Rochester, Minnesota, United States
Maximum Tolerated Dose (MTD) of DMOT4039A
Time frame: Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Recommended Phase 2 Dose (RP2D) of DMOT4039A
Time frame: Days 1 to 21 of Cycle 1 (1 cycle=21 days)
Area Under the Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUC [0-inf]) of DMOT4039A Total Antibody
Time frame: Q3W: Pre-infusion (0 hours [hrs]), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion, 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Antibody-Conjugated Monomethyl Auristatin E (acMMAE)
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
AUC (0-inf) of Unconjugated MMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Maximum Observed Concentration (Cmax) of DMOT4039A Total Antibody
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
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Unnamed facility
Amsterdam, Netherlands
Unnamed facility
Groningen, Netherlands
Cmax of acMMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Cmax of Unconjugated MMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Total Clearance (CL) of DMOT4039A Total Antibody
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
CL of acMMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Half-life (t1/2) of DMOT4039A Total Antibody
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
t1/2 of acMMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
t1/2 of Unconjugated MMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Volume of Distribution at Steady State (Vss) of DMOT4039A Total Antibody
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Vss of acMMAE
Time frame: Q3W: Pre-infusion (0 hrs), 0.5, 4, 24, 48 hrs, and 7, 9/10, 14, 16/17 days post-infusion in Cycle 1; Q1W: Pre-infusion (0 hrs), 0.5, 48 hrs post Day 1, 8, 15 infusions, 4, 24 hrs post Day 1 infusion in Cycle 1 (Infusion length=1.5 hrs) (1 cycle=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)
Time frame: Baseline (pre-infusion [0 hrs] on Day 1 Cycle 1); Post-Baseline (assessed at pre-infusion [0 hrs] on Day 1 of Cycles 2-4 and at study completion/early termination [up to 30 days after Cycle 32]) (1 cycle=21 days)
Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Time frame: Baseline up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Duration of Objective Response (DOR) According to RECIST v1.1
Time frame: From the date of initial PR or CR up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up to 30 days after Cycle 32]) (1 cycle=21 days)
Progression-free Survival (PFS) According to RECIST v1.1
Time frame: Day 1 up to PD or death, whichever occurred first (assessed at Day 1, every 2 cycles thereafter [Cycles 2, 4, 6, 8, 10, 12, 14, and 16]; at study completion/early withdrawal [up 30 days after Cycle 32]) (1 cycle=21 days)