A Phase 1/2, open label, first-in-human, dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of SAR445877 administered as monotherapy or in combination with other anticancer therapies in adults with advanced solid tumors

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 is available or is not in the best interest of the participant
2. Dose escalation Part 1B
• Participants with advanced unresectable or metastatic melanoma, NSCLC; renal cell carcinoma (RCC); HCC, colorectal cancer (MSI-H/dMMR), malignant pleural mesothelioma or esophageal squamous cell carcinoma (ESCC). and for who, in the judgement of the investigator, no standard alternative therapy is available or is not in the best interest of the participant.
3. Dose escalation Part 1C
• Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic colorectal cancer
• Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment.
4. Dose expansion/optimization Part 2

Cancer diagnosis:

• Participants in Cohorts A1 and A2 (Part 2A): Histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
• Participants in Cohort B (part 2A): 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 participants (participants without cirrhosis must have had histological confirmation of diagnosis)
• Participants in Cohorts C1 and C2 (part 2A):
• Histologically or cytologically confirmed diagnosis of advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 & 3 gastro esophageal junction (GEJ) adenocarcinoma
• Disease with any CPS scoring. No need for CPS determination at local laboratory
• 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.
• 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.
• Participants in Part 2A Cohorts E1 and E2, Part 2B Cohort E3 and Part 2D Cohorts H1 and H2: Histologically or cytologically confirmed diagnosis of advanced 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 Cohorts H1 and H2: Participants with RAS-mutant and BRAF-mutant colorectal cancer are eligible for enrollment.
• Part 2C Cohorts G1, G2 and G3: Participants with histologically confirmed unresectable 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 1 systemic therapy for the metastatic setting and must not be amenable to the available SOC.
• Participants in Cohort B: Participants who have received at least 1 prior anticancer therapy, including an anti-PD1/PD-L1 containing regimen, and for whom have progressed after a primary or secondary resistance to an anti-PD1/PD-L1.
• Participants in Cohorts C1 and C2: Participants should have failed or relapsed after at least 1 prior line of treatment which may or may not include an anti-PD1/PD-L1-based treatment depending on local standard of care.
• Participants in Cohort D: Participants must have received at least 1 systemic therapy for their advanced/ metastatic setting and must not be amenable to the available SOC.
• Participants in Part 2A Cohorts E1 and E2 and Part 2D Cohorts H1 and H2 should have failed or relapsed on at least 2 prior regimens.
• Participants in cohort E3 should have failed or relapsed on at least 1 prior regimen. Participants who have received cetuximab or other anti-EGFR therapy as part of their prior line of treatment are eligible.
• Part 2C Cohorts G1, G2 and G3: Participants must have received at least one prior line of therapy for advanced/metastatic melanoma and/or does not have any standard of care (SoC) treatment option or decline or is intolerant to be treated 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.

• 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.