A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors
- Registration Number
- NCT05584670
- Lead Sponsor
- Sanofi
- Brief 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: 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 291 participants will be exposed to the study intervention: approximately 75 participants in part 1, up to 210 participants in expansion/dose optimization part (part 2) and up to 6 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 291
-
Dose escalation Part 1 and Japan Cohort F
- Participants with advanced unresectable or metastatic solid tumors for which, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant
-
Dose expansion/optimization Part 2
Cancer diagnosis:
- Participants in Cohorts A1 and A2: Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
- Participants in Cohort B: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic hepatocellular carcinoma (HCC), or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants (participants without cirrhosis must have had histological confirmation of diagnosis)
- Participants in Cohorts C1 and C2: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3 gastro esophageal junction (GEJ) adenocarcinoma
- For participants in Cohorts C1 and C2: Disease with any CPS scoring. No need for CPS determination at local laboratory)
- For participants in Cohorts C1 and C2: Participants must have MSI (metastatic microsatellite instability) or MMR (mismatch repair) status known or determined locally and must have non-MSI-H or proficient MMR (pMMR) disease to be eligible.
- For participants in Cohorts C1 and C2: Participants with unknown HER2/neu status must have their HER2/neu status determined locally. Participants with HER2/neu negative are eligible. Participants with HER2/neu positive tumors must have documentation of disease progression on treatment containing an approved HER2 targeted therapy to be eligible.
Measurable Disease:
- At least 1 measurable lesion per RECIST 1.1 criteria
Participants in Cohorts E1, E2 and E3
- Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic colorectal cancer
- Participants must have MSI status known or determined locally and must have non-MSI-H disease to be eligible.
- Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment.
Capable of giving signed informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≥2.
- Predicted life expectancy ≤3 months.
- For participants with HCC- Cohort B (Part 2): Child Pugh Class B or C liver score. Participants with Child Pugh Class B-7 score are allowed for Part 1.
- Diagnosed of any other malignancies, either progressing or requiring active treatments, within 2 years prior to enrollment.
- Known active brain metastases or leptomeningeal metastases.
- History of treatment-related immune-mediated (or immune-related) AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents and anti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were Grade 4 in severity or have not resolved to Grade ≤1.
- Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or an anti-inflammatory equivalent) within 1 week prior to the first dose of the study medicine.
- Any clinically significant cardiac (including valvular) or vascular (thromboembolic disorders) disease, within 6 months prior to the first IMP administration.
- Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events.
- Has a known history or any evidence of interstitial lung disease or active, non-infectious pneumonitis within 3 years prior to the first dose of the study drug.
- Organ transplant requiring immunosuppressive treatment.
- Uncontrolled or active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, or has a diagnosis of immunodeficiency.
NOTE: Other Inclusion/Exclusion criteria may apply.
The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SAR445877 Expansion/Optimization Phase: Cohort E3 (Part 2B) Cetuximab SAR445877 will be administered IV in combination with cetuximab in participants with colorectal cancer (CRC). SAR445877 Japan Cohort F SAR445877 SAR445877 monotherapy will be administered intravenously in participants with advanced unresectable or metastatic solid tumor, from Japan. SAR445877 Expansion/Optimization Phase: Cohort E3 (Part 2B) SAR445877 SAR445877 will be administered IV in combination with cetuximab in participants with colorectal cancer (CRC). SAR445877 Escalation Phase (Part 1) SAR445877 SAR445877 monotherapy will be administered intravenously in participants with solid tumors over a 14-day cycle. SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A) SAR445877 SAR445877 monotherapy will be administered intravenously (IV) in participants with non-small cell lung cancer (NSCLC). SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A) SAR445877 SAR445877 monotherapy will be administered intravenously in participants with non-small cell lung cancer (NSCLC). SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with hepatocellular carcinoma (HCC). SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ). SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ). SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with immune infiltrated tumor type. SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with colorectal cancer (CRC). SAR445877 Expansion/Optimization Phase: Cohort E2 (Part 2A) SAR445877 SAR445877 monotherapy will be administered IV in participants with colorectal cancer (CRC).
- Primary Outcome Measures
Name Time Method Dose escalation and Japan Cohort F: Presence of dose-limiting toxicities (DLTs) in Cycles 1 and 2 Cycles 1 & 2 - 14 days per cycle DLTs will be defined using NCI CTCAE version 5.0 or ASTCT criteria for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS)
Dose escalation and Japan Cohort F: Percentage of participants experiencing treatment-emergent adverse events (TEAEs) The time from the first dose of study interventions up to 30 days after last dose of study interventions 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
Dose expansion/optimization: Objective response rate (ORR) From baseline to the end of dose expansion/optimization (up to 2 years) 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
- Secondary Outcome Measures
Name Time Method Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Cmax Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) Maximum plasma concentration observed
Dose escalation and Japan Cohort F: Objective response rate (ORR) From baseline to the end of dose escalation (up to 2 years) 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
Dose escalation, expansion/optimization and Japan Cohort F: Duration of response (DoR) From baseline to the end of study (up to 2 years) 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
Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 AUClast Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) Area under the serum concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast)
Dose escalation, expansion/optimization and Japan Cohort F: Assessment of SAR445877 Tmax Cycle 1 Day 1 to Day 8 or Day 14 (cycle duration of 14 days) First time to reach Cmax
Part 2b Combination: Assessment of Cetuximab serum concentration Day 1 of each cycle to cycle 4 (cycle duration of 14 days) Pre-dose concentration
Dose escalation, expansion/optimization and Japan Cohort F: Percentage of participants with presence of anti-drug antibodies (ADAs) to SAR445877 From the first dose of Cycle 1 to 30 days after last dose of study interventions (cycle duration of 14 days) Percentage of participants with anti-drug antibodies (ADAs) to SAR445877
Dose expansion/optimization: Time to response From baseline to end of dose expansion/optimization (up to 2 years) 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
Dose expansion/optimization: Clinical Benefit Rate From baseline to end of dose expansion/optimization (up to 2 years) 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
Dose expansion/optimization: Progression-free survival From baseline to end of dose expansion/optimization (up to 2 years) 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
Dose expansion/optimization: Overall survival From baseline to end of dose expansion/optimization (up to 2 years) Overall survival (OS) is defined as the time from the first dose of IMP to the date of death due to any cause.
Dose expansion/optimization: Number of participants with Adverse events (AE) The time from the first dose of study interventions up to 30 days after last dose of study interventions. 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
Trial Locations
- Locations (14)
Barbara Ann Karmanos Cancer Institute- Site Number : 8400006
🇺🇸Detroit, Michigan, United States
Fred Hutchinson Cancer Center - 825 Eastlake Ave E- Site Number : 8400010
🇺🇸Seattle, Washington, United States
Investigational Site Number : 3760004
🇮🇱Be'er Ya'akov, Israel
Investigational Site Number : 3760001
🇮🇱Tel-Aviv, Israel
University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008
🇺🇸Fairway, Kansas, United States
John Theurer Cancer Center Site Number : 8400001
🇺🇸Hackensack, New Jersey, United States
Rhode Island Hospital Site Number : 8400004
🇺🇸Providence, Rhode Island, United States
University of Texas MD Anderson Cancer Center Site Number : 8400005
🇺🇸Houston, Texas, United States
Hadassah Medical Center - PPDS_Investigational Site Number : 3760005
🇮🇱Jerusalem, Israel
Sheba Medical Center - PPDS_Investigational Site Number : 3760003
🇮🇱Ramat Gan, Israel
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis_Investigational Site Number : 5280001
🇳🇱Amsterdam, Noord-Holland, Netherlands
Erasmus MC_Investigational Site Number : 5280003
🇳🇱Rotterdam, Netherlands
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON_Investigational Site Number : 7240007
🇪🇸Barcelona, Spain
START MADRID_Hospital Universitario HM Sanchinarro - CIOCC_Investigational Site Number : 7240005
🇪🇸Madrid, Spain