Study of SAR444881 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors
- Conditions
- NeoplasmCancer
- Interventions
- Registration Number
- NCT04717375
- Lead Sponsor
- Sanofi
- Brief Summary
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.
- Detailed Description
Estimated Study Duration:
Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 125
- Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
- Histologic confirmation of malignancy
- Measurable disease per RECIST v1.1
- Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
- Participants must have adequate organ function as defined by laboratory tests
- Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
- Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma
- Active, known or suspected autoimmune disease
- Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
- Brain or leptomeningeal metastases
- Known history of positive test for HIV
- Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
- Participants after solid organ or allogeneic hematopoietic stem cell transplant
- History of life-threatening toxicity related to prior immune therapy
- History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
- Unstable or deteriorating cardiovascular disease within the previous 6 months
- Any major surgery within 4 weeks of study drug administration
- Prior/Concomitant Therapy:
- Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
- Use of other investigational drugs within 28 days
- Prior treatment with macrophage or natural killer (NK) cells activating therapies
- Administration of a live attenuated vaccine within 28 days
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SAR444881 Dose Escalation (Sub-Part 1A) SAR444881 Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 will be administered intravenously (IV), every 2 weeks (Q2W). SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B) SAR444881 Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W). SAR444881 Dose Expansion (Sub-Part 2B) SAR444881 The indication for this monotherapy cohort is cholangiocarcinoma. Enrollment will be opened based on emerging data from the dose-escalation phase and combination optimization data. SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C) SAR444881 Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W). SAR444881 Dose Optimization (Sub-Part 2A) SAR444881 SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C. SAR444881 in Combination with Pembrolizumab Dose Escalation (Sub-Part 1B) Pembrolizumab Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and pembrolizumab will be administered intravenously (IV), every 3 weeks (Q3W). SAR444881 in Combination with Cetuximab Dose Escalation (Sub-Part 1C) Cetuximab Standard "3 + 3" dose escalation design with enrollment of at least 3 participants per dose level cohort. SAR444881 and cetuximab will be administered intravenously (IV), every 2 weeks (Q2W). SAR444881 Dose Optimization (Sub-Part 2A) Cetuximab SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C. SAR444881 Dose Optimization (Sub-Part 2A) Carboplatin SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C. SAR444881 Dose Optimization (Sub-Part 2A) Pembrolizumab SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C. SAR444881 Dose Optimization (Sub-Part 2A) Pemetrexed SAR444881 Dose Optimization in combination with pembrolizumab/carboplatin/pemetrexed, pembrolizumab, or cetuximab. The indication for the combination cohorts will be non-squamous non-small cell lung cancer (NSCLC), gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), colorectal carcinoma (CRC) any RAS. Enrollment will start after the recommended dose(s) of SAR444881 have been determined based on data from Sub-Parts 1A, 1B, and 1C.
- Primary Outcome Measures
Name Time Method Part 1: Incidence of treatment-emergent adverse events and serious adverse events Through study completion, an average of 5 months Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT) Cycle 1 (28 days) Incidence of TEAEs meeting protocol defined DLT criteria
Part 2: Objective Response Rate (ORR) per RECIST v1.1 Through study completion, an average of 3 months Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
- Secondary Outcome Measures
Name Time Method Part 1: Incidence of anti-drug antibodies (ADA) Through study completion, an average of 5 months Part 1: Serum concentration at the end of the dosing interval (Ctrough) Through study completion, an average of 2 months Part 1: Objective Response Rate (ORR) per RECIST v1.1 Through study completion, an average of 3 months Proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1
Part 1: Terminal elimination half-life [T1/2] Through study completion, an average of 2 months Part 1: Area under the plasma concentration-time curve [AUC] Through study completion, an average of 2 months Part 2: Progression Free Survival (PFS) Up to 24 months 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.
Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events Through study completion, an average of 6 months Part 2: Ctrough Through study completion, an average of 3 months Part 1: Maximum observed plasma concentration [Cmax] Through study completion, an average of 2 months Part 1: time of maximum observed serum concentration (Tmax) Through study completion, an average of 2 months PFS rate At 3, 6, 9, and 12 months, and up to 24 months Percentage of participants with PFS, per RECIST v1.1
Part 2: AUC Through study completion, an average of 3 months Part 2: Duration of Response Through study completion, an average of 6 months Duration between first documentation of CR or PR to first documentation of disease progression or death due to any cause, whichever occurs first
Part 2: Cmax Through study completion, an average of 3 months Part 2: Tmax Through study completion, an average of 3 months Part 2: T1/2 Through study completion, an average of 3 months Part 2: Incidence of ADA Through study completion, an average of 6 months
Trial Locations
- Locations (18)
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
Scroll for more (8 remaining)Mayo Clinic Hospital- Site Number : 8400003🇺🇸Phoenix, Arizona, United States