This open-label, multicenter, phase 1b study will evaluate the safety and pharmacokinetics of DNIB0600A in participants with platinum-sensitive ovarian cancer (PSOC) or Non-Squamous Non-small Cell Lung Cancer (NSCLC). The maximum tolerated dose of intravenously infused DNIB0600A in combination with carboplatin will be determined in escalating dose cohorts. The combination of DNIB0600A and carboplatin will then be evaluated with and without bevacizumab \[Avastin\] in three dose expansion cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Bevacizumab 15 milligrams per kilogram (mg/kg) administered via IV infusion on Day 1 of each 21-day cycle until disease progression or death, whichever occurs first.
Carboplatin fixed dose of AUC=6 mg/mL\*min administered by IV infusion on Day 1 of each 21-day dose escalation and expansion cycles. Carboplatin will be administered for a maximum of 6 cycles or until disease progression or unacceptable toxicity, whichever is first.
DNIB0600A at an initial dose of 1.2 mg/kg will be administered via IV infusion further following a dose-escalation until DLT under consultation of the investigator on Day 1 of 21 day dose-escalation cycle. RP2D will be administered further in dose-expansion for until disease progression or death, whichever occurs first.
Massachusetts General Hospital.
Boston, Massachusetts, United States
Dana Farber Cancer Inst.
Boston, Massachusetts, United States
The University of Oklahoma
Oklahoma City, Oklahoma, United States
The Sarah Cannon Research Inst
Nashville, Tennessee, United States
Number of Participants with Dose-limiting Toxicities (DLTs)
Time frame: 21 days
Number of Participants with Adverse events (AE) and Serious Adverse Events (SAEs)
Time frame: Day 1 until 30 days after the last-infusion (up to approximately 3 years)
Number of Participants with Anti-DNIB0600A Antibodies
Time frame: Pre-infusion (0 hour) at Day 1 of Cycle 1, 2, 3, 4 (each cycle of 21 days), 30 days after last infusion (up to approximately 3 years)
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - inf)] of DNIB0600A
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Maximum Observed Plasma Concentration (Cmax)
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Minimum Observed Plasma Trough Concentration (Cmin)
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Systemic Clearance (CL)
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Volume of Distribution at Steady State (Vss)
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Plasma Decay Half-Life (t1/2)
Time frame: Pre-infusion (0 hour), hour 0.5,1 post-infusion Cycle 1 (each cycle= 28 days); 7, 14 days post-infusion of Cycle 1 (Day 8, 15 respectively); Day 1 of Cycle 2 and subsequent cycles up to last dose; 30 days after last dose (up to approximately 3 years)
Percentage of Participants With Objective Response as Assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Time frame: From screening thereafter every 2 cycles (from Cycle 2 to Cycle 16) or every 4 cycles (from Cycle 10) until disease progression or death (up to approximately 3 years)
Duration of Objective Response Rate as Assessed by RECIST v1.1
Time frame: From screening thereafter every 2 cycles (from Cycle 2 to Cycle 16) or every 4 cycles (from Cycle 10) until disease progression or death (up to approximately 3 years)
Progression Free Survival (PFS) as Assessed by RECIST v1.1
Time frame: Day 1 to the first occurrence of disease progression or death within 30 days of the last administration of study drug, whichever occurs first (up to approximately 3 years)
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