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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
542
Concentrate for solution for infusion
Solution for infusion
Solution for infusion
Solution for infusion
Solution for infusion
Solution for infusion
Christiana Care Health System- Site Number : 8400011
Newark, Delaware, United States
RECRUITINGUniversity of Iowa- Site Number : 8400014
Iowa City, Iowa, United States
RECRUITINGUniversity of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008
Fairway, Kansas, United States
RECRUITINGBarbara Ann Karmanos Cancer Institute - Detroit- Site Number : 8400006
Detroit, Michigan, United States
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)
Dose escalation and Japan Cohort F: 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 escalation (up to 2 years)
Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR)
DoR is defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) determined by Investigator per RECIST 1.1 or death from any cause, whichever occurs first
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
Maximum plasma concentration observed
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
Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)
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
First time to reach Cmax
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 to response is defined as the time from the first administration of investigational medicinal product (IMP) to the first documented evidence of confirmed PR or CR determined by Investigator per RECIST 1.1
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Clinical Benefit Rate
Clinical Benefit Rate including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator per RECIST 1.1
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Progression-free survival
PFS is defined as the time from the date of first administration of IMP to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 or death from any cause, whichever occurs first
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Overall survival
Overall survival (OS) is defined as the time from the first dose of IMP to the date of death due to any cause.
Time frame: From baseline to end of dose expansion/optimization (up to 2 years)
Dose expansion/optimization: Number of participants with Adverse events (AE)
Presence of adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 or 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.
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John Theurer Cancer Center Site Number : 8400001
Hackensack, New Jersey, United States
RECRUITINGNYU Langone Medical Center-New York- 550 1st Ave - BRANY - PPDS- Site Number : 8400013
New York, New York, United States
RECRUITINGRhode Island Hospital Site Number : 8400004
Providence, Rhode Island, United States
RECRUITINGUniversity of Texas MD Anderson Cancer Center Site Number : 8400005
Houston, Texas, United States
RECRUITINGFred Hutchinson Cancer Center - 825 Eastlake Ave E- Site Number : 8400010
Seattle, Washington, United States
RECRUITINGServicios Médicos URUMED SpA_Investigational Site Number : 1520002
Rancagua, General Bernardo O'Higgins, Chile
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