This phase I trial is evaluating the combination of two targeted therapies (SAR439459 alone and in combination with Cemiplimab) in adult patients that have advanced solid cancersA Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination With Cemiplimab in Adult Patients With Advanced Solid Tumors

Exclusion

• Age <18 years or < the country's legal age of majority if the legal age is more than 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status >1.
• Concurrent treatment with any other anticancer therapy (including radiotherapy or investigational agents) or participation in another clinical study.
• Washout period of less than 3 weeks to prior anticancer therapy.
• Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy by using highly effective contraceptive.
• Pregnant or breast-feeding women.
• Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Significant and uncontrolled concomitant illness, including any psychiatric condition.
• Active infections, including unexplained fever (temperature >38.1ºC), or antibiotic therapy within 1 week prior to enrollment.
• Any prior organ transplant including allogeneic bone marrow transplant.
• History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• History of known human immunodeficiency virus (HIV), HIV serology at screening will be conducted only for patients in German study sites.
• Known uncontrolled hepatitis B virus (HBV) infection.
• Known untreated current hepatitis C virus (HCV) infection.
• Any major surgery within the last 28 days.
• Patients with primary central nervous system (CNS) tumors and/or CNS metastases of non-CNS primary tumors.
• History of congestive heart failure, myocardial infarction with reduced ejection fraction, symptomatic coronary artery disease, documented uncontrolled hypertension, major clinically significant Electrocardiography (ECG) and echocardiogram abnormalities, significant ventricular arrhythmias, significant valvular heart disease (including valve replacement), vascular malformation, aneurysm, significant pulmonary conditions such as idiopathic pulmonary hypertension, uncontrolled chronic lung disease.
• History of severe, acute or chronic renal diseases.
• Any of the following within 6 months prior to study enrollment: pulmonary embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage.
• Inadequate hematological, renal or liver function.
• Non-resolution of any prior treatment related toxicity to Grade <2.
• Prior treatment with any anti-transforming growth factor β (anti-TGFβ) inhibitors.
• Known allergies to any component of SAR439459 and/or cemiplimab.
• Patients with uveal melanoma and patients with prior or ongoing uveitis.
• Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of SAR439459 and/or cemiplimab (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).
• History of interstitial lung disease or active non-infectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
• Patients with underlying cancer predisposition syndromes.
• Receipt of a live vaccine within 30 days of planned start of study medication.
• Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the first dose of SAR439459.
• Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of normal (ULN).
• Patients accommodated in an institution because of regulatory or legal order; prisoners or patients who are legally institutionalized.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.