A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol)

• Status: Not yet recruiting
• Trial end date: 2023-07-25
• Target enrollment: 0
• Participant gender: All

Summary

The study is a phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with other anticancer therapies for the treatment of participants aged 18 years and older with advanced and metastatic gastrointestinal cancer. This study is structured as a master protocol for the investigation of SAR444245 with other anticancer therapies.

Sub study 01 - Cohort A aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic ESCC.

Sub study 02 - Cohort B1, B2 and B3 would focus on non MSI-H tumors with a large unmet need to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma (GC/GEJ), especially with low PD-L1 expression or after progression on prior PD1/PD-L1-based regimens.

Sub study 03 - Cohort C aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with the anti-PD1 antibody pembrolizumab will result in a significant increase in the percentage of patients experiencing an objective response in participants with advanced unresectable or metastatic HCC who relapsed on prior PD1/PD-L1-based regimens.

Sub study 04 - Cohort D1 and D2 aims to establish proof-of-concept that combining the non-alpha-IL2 SAR444245 with either the anti-PD1 antibody pembrolizumab or with the anti-EGFR IgG1 antibody cetuximab will result in a significant increase in the percentage of patients experiencing an objective response in the setting of advanced unresectable or mCRC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Cetuximab; Pembrolizumab

Criteria

Inclusion Criteria:

• Participant must be ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent.

• Participants with:

Sub-study01: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic esophageal cancer of the squamous cell carcinoma subtype

Sub-study02: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 & 3 GEJ.

Sub-study03: Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic HCC, or clinically by AASLD criteria in cirrhotic patients.

Sub-study04: Histologically or cytologically confirmed diagnosis of advanced unresectable or mCRC. Only patients with non-MSI-H disease are eligible.

• Participants (all sub-studies) must have at least one measurable lesion Mandatory baseline biopsy for the first 20 participants to enroll in sub-study01, sub-study02 and sub-study04. On-treatment biopsy for at least 20 participants in sub-study04. On-treatment biopsies are otherwise optional per Investigator's discretion for the other cohorts.

• Females are eligible to participate if they are not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees:

• to use approved contraception method and submit to regular pregnancy testing prior to treatment and for at least 180 days after discontinuing study treatment and to refrain from donating or cryopreserving eggs for 180 days after discontinuing study treatment.

• Males are eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment.

• Capable of giving signed informed consent

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of ≥2

• Poor organ function

• Active brain metastases or leptomeningeal disease.

• History of allogenic or solid organ transplant.

• Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery within 28 days prior to first IMP administration

• Comorbidity requiring corticosteroid therapy

• Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP

• Severe or unstable cardiac condition within 6 months prior to starting study treatment

• Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years

• Participants with baseline SpO2 ≤92% (without oxygen therapy). - Participant has received prior IL2-based anticancer treatment.

• Participants on sub-study02 cohort B1 and B2 or sub-study 04 - cohort D1 with prior treatment with an agent that blocks the PD-1/PD-L1 pathway.

• Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.