A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors
Purpose
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 285 participants will be enrolled to the study intervention: approximately 75 participants in part 1 and up to 210 participants in expansion/dose optimization part (part 2).
Condition
- Solid Tumor
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Dose escalation Part 1 - 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 2. 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 patients (patients 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 CPS scoring of <1 as determined at local laboratory with an Agency approved test (for the other cohorts: 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.
Exclusion Criteria
- 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
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental SAR445877 Escalation Phase (Part 1) |
SAR445877 monotherapy will be administered intravenously in patients with solid tumors over a 14-day cycle. |
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|
Experimental SAR445877 Expansion/Optimization Phase: Cohort A1 (Part 2A) |
SAR445877 monotherapy will be administered intravenously (IV) in patients with non-small cell lung cancer (NSCLC). |
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|
Experimental SAR445877 Expansion/Optimization Phase: Cohort A2 (Part 2A) |
SAR445877 monotherapy will be administered intravenously in patients with non-small cell lung cancer (NSCLC). |
|
|
Experimental SAR445877 Expansion/Optimization Phase: Cohort B (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with hepatocellular carcinoma (HCC). |
|
|
Experimental SAR445877 Expansion/Optimization Phase: Cohort C1 (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ). |
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|
Experimental SAR445877 Expansion/Optimization Phase: Cohort C2 (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with gastric cancer/gastro esophageal junction adenocarcinoma (GC/GEJ). |
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Experimental SAR445877 Expansion/Optimization Phase: Cohort D (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with immune infiltrated tumor type. |
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|
Experimental SAR445877 Expansion/Optimization Phase: Cohort E1 (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with colorectal cancer (CRC). |
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Experimental SAR445877 Expansion/Optimization Phase: Cohort E2 (Part 2A) |
SAR445877 monotherapy will be administered IV in patients with colorectal cancer (CRC). |
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|
Experimental SAR445877 Expansion/Optimization Phase: Cohort E3 (Part 2B) |
SAR445877 will be administered IV in combination with cetuximab in patients with colorectal cancer (CRC). |
|
Recruiting Locations
University of Kansas Cancer Center Clinical Research Center (Fairway) Site Number : 8400008
Fairway, Kansas 66205-2528
Fairway, Kansas 66205-2528
More Details
- Status
- Recruiting
- Sponsor
- Sanofi
Study Contact
Trial Transparency email recommended (Toll free for US & Canada)800-633-1610
contact-us@sanofi.com
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.