The primary objective of Part A is to evaluate the safety and tolerability of S-531011 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of S-531011 with or without pembrolizumab. The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D with or without pembrolizumab. The primary objective of Parts D and E is to evaluate the antitumor activity of S-531011 at the RP2D in combination with bevacizumab with our without pembrolizumab.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
282
Administered by intravenous infusion
Administered by intravenous infusion
Administered by intravenous infusion
Angeles Clinic and Research Center
Los Angeles, California, United States
ACTIVE_NOT_RECRUITINGUniversity of Florida Health
Gainesville, Florida, United States
RECRUITINGHenry Ford Health Center
Detroit, Michigan, United States
ACTIVE_NOT_RECRUITINGFox Chase Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGNational Cancer Center Hospital East
Kashiwa, Chiba, Japan
RECRUITINGThe University of Osaka Hospital
Suita, Osaka, Japan
RECRUITINGNational Cancer Center Hospital
Chuo Ku, Tokyo, Japan
RECRUITINGPart A: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Approximately 12 months (Part A-1); Approximately 24 months (Part A-2)
Parts B, C, D, E: Objective Response Rate
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Parts B, C, D, E: Duration of Response
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Parts B, C, D, E: Disease Control Rate
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Parts B, C, D, E: Time to Response
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Parts B, C, D, E: Progression-free Survival
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Parts B, C, D, E: Overall Survival
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])
Part A: Objective Response Rate
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])
Part A: Duration of Response
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])
Part A: Disease Control Rate
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])
Part A: Time to Response
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])
Part A: Progression-free Survival
Time frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])
All Parts: Serum concentrations of S-531011
Time frame: Part A: Cycle 1, Days 8 and 15 (4 hours post infusion); Cycles 2-9, Day 1 (pre- and end-of-infusion); Safety Follow-up Visit. Parts B, C, D, E: Day 1 of Cycles 1-9 (pre- and end-of-infusion); Safety Follow-up Visit. (each cycle is 21 days)
Part A: Maximum Serum Concentration (Cmax) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Time to Maximum Serum Concentration (Tmax) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Area Under the Concentration-time Curve from Time Zero to the Time of Last Quantifiable Concentration After Dosing (AUC0-last) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Area Under the Concentration-time Curve Extrapolated from Time Zero to Infinity (AUC0-inf) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Terminal elimination rate constant (λz) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Terminal Elimination Half-life (t1/2,z) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Total Clearance (CL) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Volume of Distribution at Steady State (Vss) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
Part A: Mean Residence Time (MRT) of S-531011
Time frame: Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days)
All Parts: Anti-S-531011 Antibody (ADA) Titer Level
Time frame: Day 1 of Cycles 1 to 9 (each cycle is 21 days)
All Parts: Anti-S-531011 Antibody (ADA) Titer Level
Neutralization assays will be performed only for the samples that are confirmed to have ADA.
Time frame: Day 1 of Cycles 1 to 9 (each cycle is 21 days)
All Parts: Changes in serum tumor markers from pretreatment to on-treatment
Time frame: Baseline and Day 1 of each treatment cycle (each cycle is 21 days)
Parts B, C, D, E: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Approximately 12 months (Part B); Approximately 24 months (Parts C, D, E)
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