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 with advanced and metastatic gastrointestinal cancer

Main protocol:
-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.
-Capable of giving signed informed consent
-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 after discontinuing study treatment
- 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 after
discontinuing study treatment.

Sub-study01:
-Histologically or cytologically confirmed diagnosis of advanced unresectable
or metastatic esophageal cancer of the squamous cell carcinoma subtype
-MSI status: Participants must have either unknown MSI status or if MSI status
is known, participants must have non-MSI-H disease to be eligible.
-Prior anticancer therapy: Participants should have received at least one but
no more than 2 prior lines of treatment, including an anti-PD-1/PDL-1
containing regimen and have progressed after a primary or secondary resistance
to an anti-PD-1/PDL-1.

-Sub-study02:
-Histologically or cytologically confirmed diagnosis of advanced unresectable
or metastatic gastric cancer or Siewert Type 2 & 3 GEJ.
-PD-L1 expression using CPS as determined at local laboratory with an approved
test
-MSI status: Participants must have MSI status known, determined locally and
must have non-MSI-H disease to be eligible.
-HER2/neu status: 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 trastuzumab to be eligible.
-Prior anticancer therapy: Participants could be anti-PD-1/PDL-1 naïve (cohort
B1 and B2) or have received an anti-PD-1/PDL-1 before (cohort B3)

Participants (all sub-studies) must have at least one measurable lesion.
Mandatory baseline biopsy for the first 20 participants to enroll in substudy01
and sub-study02 .

- Eastern Cooperative Oncology Group (ECOG) performance status of >=2
- Predicted life expectancy <=3 months
- 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
-History of pneumonitis, interstitial lung disease, HIV infection, uncontrolled
hepatitis B infection,
- 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
- Known second malignancy either progressing or requiring active treatment
within the
last 3 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