The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization/expansion phase (Part 2). Part 1 is comprised of three sub-parts: SAR444881 administered alone (Sub-Part 1A), SAR444881 administered in combination with pembrolizumab (Sub-Part 1B), and SAR444881 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of SAR444881 per indication are administered in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed (Sub-Part 2A); and a dose expansion part where SAR444881 is administered alone (Sub-Part 2B). In Sub-Part 2A, a two-stage design will be implemented to conduct dose optimization for each indication with combination therapy- Stage 1 (Preliminary Assessment) and Stage 2 (Randomization). Study is non-randomized except Stage 2 of Sub-Part 2A which will use randomization.
Estimated Study Duration: Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
125
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Concentrate for solution for infusion; Route of administration: Intravenous
Pharmaceutical form: Powder for concentrate for solution for infusion or concentrate for solution for infusion; Route of administration: Intravenous
Mayo Clinic Hospital- Site Number : 8400003
Phoenix, Arizona, United States
City of Hope Comprehensive Cancer Center- Site Number : 8400002
Duarte, California, United States
University of Colorado- Site Number : 8400012
Aurora, Colorado, United States
Smilow Cancer Center at Yale-New Haven- Site Number : 8400001
New Haven, Connecticut, United States
Clermont Oncology Center- Site Number : 8400005
Clermont, Florida, United States
Mid Florida Hematology and Oncology Center- Site Number : 8400006
Orange City, Florida, United States
Mercy Cancer Center - MercyOne Richard Deming Cancer Center- Site Number : 8400011
Des Moines, Iowa, United States
Norton Cancer Institute - Downtown Women's Cancer Center- Site Number : 8400004
Louisville, Kentucky, United States
Mayo Clinic Hospital Rochester- Site Number : 8400007
Rochester, Minnesota, United States
Investigational Site Number : 1240001
Barrie, Ontario, Canada
...and 8 more locations
Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT)
Incidence of TEAEs meeting protocol defined DLT criteria
Time frame: Cycle 1 (28 days)
Part 1: Incidence of treatment-emergent adverse events and serious adverse events
Time frame: Through study completion, an average of 5 months
Part 2: Objective Response Rate (ORR) per RECIST v1.1
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Time frame: Through study completion, an average of 3 months
Part 1: Objective Response Rate (ORR) per RECIST v1.1
Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Time frame: Through study completion, an average of 3 months
Part 1: Maximum observed plasma concentration [Cmax]
Time frame: Through study completion, an average of 2 months
Part 1: Serum concentration at the end of the dosing interval (Ctrough)
Time frame: Through study completion, an average of 2 months
Part 1: time of maximum observed serum concentration (Tmax)
Time frame: Through study completion, an average of 2 months
Part 1: Terminal elimination half-life [T1/2]
Time frame: Through study completion, an average of 2 months
Part 1: Area under the plasma concentration-time curve [AUC]
Time frame: Through study completion, an average of 2 months
Part 1: Incidence of anti-drug antibodies (ADA)
Time frame: Through study completion, an average of 5 months
Part 2: Progression Free Survival (PFS)
Time from the date of first dose of study drug to the date of first documented disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 24 months
PFS rate
Percentage of participants with PFS, per RECIST v1.1
Time frame: At 3, 6, 9, and 12 months, and up to 24 months
Part 2: Duration of Response
Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first
Time frame: Through study completion, an average of 6 months
Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events
Time frame: Through study completion, an average of 6 months
Part 2: Cmax
Time frame: Through study completion, an average of 3 months
Part 2: Ctrough
Time frame: Through study completion, an average of 3 months
Part 2: Tmax
Time frame: Through study completion, an average of 3 months
Part 2: T1/2
Time frame: Through study completion, an average of 3 months
Part 2: AUC
Time frame: Through study completion, an average of 3 months
Part 2: Incidence of ADA
Time frame: Through study completion, an average of 6 months
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