A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)

Investigating an investigational medication with anticancer therapies for advanced gastrointestinal cancers

Not Recruiting
18 years or above
All
Phase 2
138 participants needed

Study Overview

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 esophageal squamous cell carcinoma (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 metastatic colorectal cancer (mCRC).

Study Details

The duration of the study for an individual patient will start from the signature of the main informed consent and include a screening period of up to 28 days, a treatment period [max 35 cycles {cohort A; B1,B2, B3, C and D1} = 735 days or until PD {cohort D2}], an end-of-treatment visit at least 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier.

Eligibility Criteria

You may be eligible for this study if you meet the following criteria:

  • Conditions: Oesophageal Squamous Cell Carcinoma, Gastric Cancer, Hepatocellular Carcinoma, Colorectal Cancer, Oesophageal Adenocarcinoma
  • Age: 18 years or above
  • Gender: All

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 hepatocellular carcinoma (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 120 days (for Cohort A, B1, B2, B3, C, and D1) or 60 days (for Cohort D2) [corresponding to the time needed to eliminate any study intervention(s)].
    • and to refrain from donating or cryopreserving eggs for 120 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 3 days [corresponding to time needed to eliminate SAR444245] after the last dose of SAR444245.

  • 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 (>10 mg prednisone/day or equivalent) within 2 weeks of IMP initiation. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder. Participants who require a brief course of steroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded).
  • 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 or live attenuated-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.

Updated on 01 Jul 2025. Study ID: NCT05104567

This study investigates an investigational medication combined with other anticancer therapies for treating adults with advanced and metastatic gastrointestinal cancers. The purpose is to assess the clinical benefits of this combination in patients with different types of gastrointestinal cancers, such as esophageal, gastric, gastro-esophageal junction, hepatocellular, and colorectal cancers. The investigational medication is being tested with antibodies that target specific proteins involved in cancer growth.

Participants in the study will undergo various procedures, including a screening period of up to 28 days and a treatment period that may last up to 735 days or until disease progression. They will receive a combination of the investigational medication and other anticancer therapies, and some participants will be required to have biopsies to assess the treatment's effects on their cancer. A placebo is not used in this study, meaning all participants will receive active treatment.

  • Who can participate: Adults aged 18 and older with advanced unresectable or metastatic gastrointestinal cancers may participate. Key eligibility includes having measurable lesions and a confirmed diagnosis of specific cancer types.
  • Study details: Participants will receive the investigational medication combined with anticancer therapies. Some participants may need to undergo biopsies, which involve removing a small tissue sample for examination, to assess the treatment's effects.