A Phase 1b/2, Multicenter, Open-label Study of S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors
Summary
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.
Arms & interventions
- DrugS-531011
Administered by intravenous infusion
- DrugPembrolizumab
Administered by intravenous infusion
- DrugBevacizumab
Administered by intravenous infusion
Outcome measures
Primary
Part 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])
Secondary
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
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)
Eligibility criteria
Study locations (5)
Angeles Clinic and Research Center
Los Angeles, California, 90025
University of Florida Health
Gainesville, Florida, 32610
Henry Ford Health Center
Detroit, Michigan, 48202
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
MD Anderson Cancer Center
Houston, Texas, 77030