A First-in-human, Dose Escalation and Dose Expansion Study of SAR445877 in Adult Participants With Advanced Solid Tumors

Inclusion Criteria:

1. Dose escalation Part 1A and Japan Cohort F

• Participants with advanced unresectable or metastatic solid tumors for which,in the judgement of the investigator, no standard alternative therapy isavailable or is not in the best interest of the participant

2. Dose escalation Part 1B

• Participants with advanced unresectable or metastatic melanoma, NSCLC; renalcell carcinoma (RCC); HCC, colorectal cancer (MSI-H/dMMR), malignant pleuralmesothelioma or esophageal squamous cell carcinoma (ESCC). and for who, in thejudgement of the investigator, no standard alternative therapy is available oris not in the best interest of the participant.

3. Dose escalation Part 1C

• Histologically or cytologically confirmed diagnosis of advanced unresectable ormetastatic colorectal cancer

• Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible forenrollment.

4. Dose expansion/optimization Part 2 Cancer diagnosis:

• Participants in Cohorts A1 and A2 (Part 2A): Histologically or cytologicallyconfirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)

• Participants in Cohort B (part 2A): Histologically or cytologically confirmeddiagnosis 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 musthave had histological confirmation of diagnosis)

• Participants in Cohorts C1 and C2 (part 2A):

• Histologically or cytologically confirmed diagnosis of advancedunresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3gastro esophageal junction (GEJ) adenocarcinoma

• Disease with any CPS scoring. No need for CPS determination at locallaboratory

• Participants must have MSI (metastatic microsatellite instability) or MMR (mismatch repair) status known or determined locally and must havenon-MSI-H or proficient MMR (pMMR) disease to be eligible.

• Participants with unknown HER2/neu status must have their HER2/neu statusdetermined locally. Participants with HER2/neu negative are eligible.Participants with HER2/neu positive tumors must have documentation ofdisease progression on treatment containing an approved HER2 targetedtherapy to be eligible.

• Participants in Part 2A Cohorts E1 and E2, Part 2B Cohort E3 and Part 2DCohorts H1 and H2: Histologically or cytologically confirmed diagnosis ofadvanced unresectable or metastatic colorectal cancer.

• Participants in Part 2A Cohorts E1, and E2 and Part 2B Cohort E3 MSI status: Participants must have MSI status known or determined locally and must have non-MSI-H disease to be eligible.

• Participants in Part 2A Cohorts E1, E2, Part 2B Cohort E3 and Part 2D CohortsH1 and H2: Participants with RAS-mutant and BRAF-mutant colorectal cancer areeligible for enrollment.

• Part 2C Cohorts G1, G2 and G3: Participants with histologically confirmedunresectable locally advanced or metastatic melanoma

5. Prior anticancer therapy (For dose expansion/optimization Part 2 only)

• Participants in Cohorts A1 and A2: Participants must have received at least 1systemic therapy for the metastatic setting and must not be amenable to theavailable SOC.

• Participants in Cohort B: Participants who have received at least 1 prioranticancer therapy, including an anti-PD1/PD-L1 containing regimen, and forwhom have progressed after a primary or secondary resistance to ananti-PD1/PD-L1.

• Participants in Cohorts C1 and C2: Participants should have failed or relapsedafter at least 1 prior line of treatment which may or may not include ananti-PD1/PD-L1-based treatment depending on local standard of care.

• Participants in Cohort D: Participants must have received at least 1 systemictherapy for their advanced/ metastatic setting and must not be amenable to theavailable SOC.

• Participants in Part 2A Cohorts E1 and E2 and Part 2D Cohorts H1 and H2 shouldhave failed or relapsed on at least 2 prior regimens.

• Participants in cohort E3 should have failed or relapsed on at least 1 priorregimen. Participants who have received cetuximab or other anti-EGFR therapy aspart of their prior line of treatment are eligible.

• Part 2C Cohorts G1, G2 and G3: Participants must have received at least oneprior line of therapy for advanced/metastatic melanoma and/or does not have anystandard of care (SoC) treatment option or decline or is intolerant to betreated with SoC treatment.

Measurable Disease:

• At least 1 measurable lesion per RECIST 1.1 criteria

Part 1C and Part 2D: Adequate coagulation function for all participants. For participants receiving anti-coagulant therapy (except platelet anti-aggregates) the adequate therapeutic levels of INR should be confirmed.

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 activetreatments, within 2 years prior to enrollment

• Known active brain metastases or leptomeningeal metastases

• History of treatment-related immune-mediated (or immune-related) AEs fromimmune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents andanti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies) that causedpermanent discontinuation of the agent, or that were Grade 4 in severity or have notresolved to Grade ≤1

• Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mgprednisone/day or an anti-inflammatory equivalent) within 1 week prior to the firstdose of the study medicine

• Any clinically significant cardiac (including valvular) or vascular (thromboembolicdisorders) disease, within 6 months prior to the first IMP administration

• Ongoing or recent (within 2 years) evidence of significant autoimmune disease thatrequired treatment with systemic immunosuppressive treatments, which may suggestrisk 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), hepatitisB, 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.