This is Phase 1/Phase 2, open label, multiple cohort, first-in-human study to evaluate safety, PK, PDy and efficacy of SAR444200 as a monotherapy or in combination with other anti-cancer agents for participants aged at least 18 years with previously treated metastatic malignancies.
Treatment Period: enrolled participants will receive continuous treatment until disease progression (PD), unacceptable adverse event (AE), or other permanent discontinuation criteria. The End of Treatment visit will occur 30 days ±7 days from last IMP administration or prior to initiation of further therapy, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Sterile lyophilized powder for solution for infusion Route of administration: intravenous (IV) infusion
concentrate for solution for infusion Route of administration: intravenous (IV) infusion
USC Norris Comprehensive Cancer Center- Site Number : 8400004
Los Angeles, California, United States
Icahn School of Medicine at Mount Sinai- Site Number : 8400005
New York, New York, United States
Part 1A and 1B: Number of participants with Dose Limiting Toxicities (DLTs)
Incidence and nature of DLTs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Time frame: For Part 1A: from the Cycle 1, Day 1 up to Day 21For Part 1B: from Cycle 2 Day 1 up to Day 21
Part 1A and 1B: Number of participants with Adverse Events (AEs)
Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: the time from the first dose of study interventions up to 30 days after last dose of study interventions
Part 2A: Objective Response Rate (ORR)
ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: From baseline to the end of expansion study (up to 2 years)
Part 1A and 1B: Objective Response Rate (ORR)
ORR defined as the proportion of participants who have a complete response (CR) or partial response (PR) determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: Baseline to end of dose escalation study (up to 2 years)
All parts: Duration of response (DoR)
DoR defined as the time from first documented evidence of confirmed CR or PR until progressive disease (PD) or death from any cause, whichever occurs first determined per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: Baseline to end of study (up to 2 years)
All parts: Assessment of PK parameters: Cmax
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Lifespan Corporation- Site Number : 8400002
Providence, Rhode Island, United States
The University of Texas MD Anderson Cancer Center- Site Number : 8400003
Houston, Texas, United States
Investigational Site Number : 1240002
Toronto, Ontario, Canada
Investigational Site Number : 1240001
Québec, Quebec, Canada
Investigational Site Number : 1560001
Shanghai, China
Investigational Site Number : 1560002
Wuhan, China
Investigational Site Number : 7020002
Singapore, Singapore
Investigational Site Number : 7020003
Singapore, Singapore
...and 3 more locations
Maximum plasma concentration observed
Time frame: Cycle 1 Day 1 to Day 21
All parts:Assessment of PK parameters: AUC0-T
Area under the concentration versus time curve calculated using the trapezoidal method during a dosing interval (T)
Time frame: Cycle 1 Day 1to Day 21
All parts: Assessment of PK parameters: Tmax
Time to reach Cmax
Time frame: Cycle 1 Day 1to Day 21
All parts: Incidence of anti-drug antibodies (ADAs) to SAR444200
Incidence of participants with anti-drug antibodies to SAR444200
Time frame: From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
All parts: Incidence of anti-drug antibodies (ADAs) to atezolizumab
Time frame: From the first dose of Cycle to 30 days after last dose of study interventions. Cycle duration is 21 days
Part 2A: Progression Free Survival (PFS)
PFS, defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator as per RECIST 1.1 (or death due to any cause, whichever occurs first)
Time frame: From baseline to end of expansion study (up to 2 years)
Part 2A: Number of participants with Adverse Events (AEs)
Incidence of treatment emergent AEs and serious adverse events (SAEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time frame: The time from the first dose of study interventions up to 30 days after last dose of study interventions.