A Phase 1/2, Open Label, First-in-human, Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR445877 Administered as Monotherapy or in Combination With Other Anticancer Therapies in Adults With Advanced Solid Tumors
Summary
This is a Phase 1/2, open label, multiple cohort study to assess the safety and preliminary efficacy of SAR445877 as a monotherapy or in combination with other anticancer therapies for participants aged at least 18 years with advanced unresectable or metastatic solid tumors. The study will include 2 parts: A dose escalation Part 1: for finding the therapeutic dose(s) of SAR445877 in a monotherapy given every 2 weeks (Q2W) or weekly (QW) and in combination with other anticancer therapies when applicable. A multicohort dose expansion/dose optimization Part 2: for the assessment of safety and preliminary efficacy of SAR445877 in monotherapy and in combination with cetuximab or with next generation aCTLA4 (ADG126) or with bevacizumab. 2 recommended doses for expansion/optimization of SAR445877 identified from dose escalation part 1 will be tested in different indications in monotherapy and in combination with other anticancer therapies as applicable. Approximately 542 participants will be exposed to the study intervention: * approximately 123 participants in part 1, * up to 410 participants in expansion/dose optimization part (part 2) * and up to 9 participants in Japan cohort F.
Detailed description
The duration of the study for a participant will include: * Screening Period: up to 28 days * Treatment Period: enrolled and exposed participants will receive continuous treatment until progressive disease (PD), or an occurrence of an unacceptable AE, a withdrawal of consent, or until other permanent discontinuation criteria described in the protocol are met. The End of Treatment (EOT) visit will occur 30 days ±7 days from the last IMP administration or prior to the initiation of further therapy, whichever occurs first. The follow-up period will occur until disease progression, the start of new anticancer therapy, death, or withdrawal of participant's consent, whichever comes first.
Arms & interventions
- DrugSAR445877
Concentrate for solution for infusion
- DrugCetuximab
Solution for infusion
- DrugADG126
Solution for infusion
- DrugBevacizumab
Solution for infusion
- DrugNivolumab
Solution for infusion
- DrugIpilimumab
Solution for infusion
Outcome measures
Primary
Dose escalation part 1A, 1C and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2
DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)
Time frame: Cycles 1 & 2 - 14 days per cycle
Dose escalation part 1B: Presence of dose-limiting toxicities (DLTs) in Cycle 1 to 3 in part B
Time frame: Cycle 1 to 3 -14 days per cycle
Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs)
Presence of TEAEs, SAEs, and lab abnormalities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions
Dose expansion/optimization: Objective response rate (ORR)
Proportion of participants who have a confirmed complete response (CR) or a partial response (PR), as the best overall response (BOR) determined by the Investigator as per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: From baseline to the end of dose expansion/optimization (up to 2 years)
Secondary
Dose escalation and Japan Cohort F: Objective response rate (ORR)
Time frame: From baseline to the end of dose escalation (up to 2 years)
Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR)
Time frame: From baseline to the end of study (up to 2 years)
Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax
Time frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUCtau
Time frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Tmax
Time frame: Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days)
Dose escalation, expansion/optimization in Combination: Assessment of combined therapies Ctrough
Time frame: Day 1 of each cycle to cycle 4 (cycle duration of 14 days)
Dose escalation, expansion/optimization and Japan Cohort F: Percentage of participants with presence of anti-drug antibodies (ADAs) against SAR445877
Time frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)
Dose escalation, expansion/optimization: Percentage of participants with presence of anti-drug antibodies (ADAs) against ADG126
Time frame: From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days)
Dose expansion/optimization: Time to response
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Clinical Benefit Rate
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Progression-free survival
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Overall survival
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Number of participants with Adverse events (AE)
Time frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions.
Eligibility criteria
Study locations (9)
Christiana Care Health System- Site Number : 8400011
Newark, Delaware, 19713-2072
University of Iowa- Site Number : 8400014
Iowa City, Iowa, 52242-1009
University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008
Fairway, Kansas, 66205-2528
Barbara Ann Karmanos Cancer Institute - Detroit- Site Number : 8400006
Detroit, Michigan, 48201
John Theurer Cancer Center Site Number : 8400001
Hackensack, New Jersey, 07601
NYU Langone Medical Center-New York- 550 1st Ave - BRANY - PPDS- Site Number : 8400013
New York, New York, 10016-6402
Rhode Island Hospital Site Number : 8400004
Providence, Rhode Island, 02903
University of Texas MD Anderson Cancer Center Site Number : 8400005
Houston, Texas, 77030-4000
Fred Hutchinson Cancer Center - 825 Eastlake Ave E- Site Number : 8400010
Seattle, Washington, 98109-4405