A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202)

Primary Objective:

-To determine the antitumor activity of SAR444245 in combination with other anticancer therapies.

Secondary Objectives:

* To confirm the dose and to assess the safety profile of SAR444245 when combined with other anticancer therapies.
* To assess other indicators of antitumor activity.
* To assess the pharmacokinetic (PK) profile of SAR444245 when given in combination with pembrolizumab.
* To assess the immunogenicity of SAR444245.

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 \[max 35 cycles {cohorts A1, A2, and B1} = 735 days or until PD {cohort C1}\], 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:
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.
* Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (cohorts A1, A2, and B1), or unresectable malignant pleural mesothelioma (cohort C1).
* Cohort A1: PD-L1 expression TPS ≥ 50%
* Cohort A2: PD-L1 expression TPS 1 - 49%
* Prior anticancer therapy
* Cohorts A1 and A2: No prior systemic therapy for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
* Cohort B1: One prior anti-PD1/PD-L1 regimen (may include chemotherapy) plus one additional chemotherapy regimen
* Cohort C1: One or two prior systemic treatments that include pemetrexed-based regimen in combination with platinum agent.
* All cohorts must have a measurable disease
* Mandatory baseline biopsy for the first 20 participants to enroll in cohorts A1, A2
* Cohort B1: Based on the Investigator's judgment, either docetaxel or pemetrexed is not the best treatment option for the participant.
* 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 150 days after discontinuing study treatment
  * to refrain from donating or cryopreserving eggs for 150 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:

Participants are excluded from the study if any of the following criteria apply:

* Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2.
* Poor bone marrow reserve
* Poor organ function
* Participants with baseline SpO2 ≤ 92%.
* Active brain metastases or leptomeningeal disease.
* History of allogenic tissue/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 or local intervention within 28 days.
* Has received prior IL-2-based anticancer treatment.
* 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
* Known second malignancy either progressing or requiring active treatment within the last 3 years
* Cohorts A1, A2, and C1: Prior treatment with an agent (approved or investigational) that blocks the PD1/PD-L1 pathway (participants who joined a study with an anti-PD1/PD-L1 but have written confirmation they were on control arm are allowed).
* 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 the potential participation in a clinical trial.