A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

A Phase 1 First-in-Human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR441000 Administered Intratumorally as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

Primary Objectives:

• Dose Escalation: To determine maximum tolerated dose (MTD) or maximum administered dose (MAD) and overall safety and tolerability profile of SAR441000 when administered intratumorally as monotherapy and in combination with cemiplimab in patients who have no alternative standard treatment options.
• Dose Expansion (Combination): To determine the objective response rate of SAR441000 administered intratumorally in combination with cemiplimab in patients with melanoma, cutaneous squamous cell carcinoma or head and neck squamous cell carcinoma.

Secondary Objectives:

• To characterize the pharmacokinetic (PK) profile of SAR441000 administered as monotherapy and in combination with cemiplimab.
• To assess the immunogenicity of SAR441000.
• To characterize the safety of SAR441000 when administered intratumorally in combination with cemiplimab.
• To determine the disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) of SAR441000.
• To determine the recommended dose of SAR441000 for the expansion phase.

The expected duration of treatment for patients who benefit from study intervention may vary, based on progression date. Median expected duration of study per patient is estimated as 9 months in monotherapy and 12 months in combination therapy.

The maximum treatment duration for non-progressive patients is up to 2 years.

Inclusion criteria:

• At least 18 years of age
• Advanced solid tumors including lymphomas for which no standard alternative therapy is available (escalation phase).
• Advanced melanoma (Stage IIIB-C or Stage IV, anti-PD-1/PD-L1 treated or not) or anti-PD-1/PD-L1 not treated advanced Head and Neck Squamous Cell Cancer or anti-PD-1/PD-L1 not treated Advanced Cutaneous Squamous Cell Cancer where no other alternative treatment option exists (expansion phases).
• Minimum 3 lesions enrollment.
• Injectable disease (i.e., suitable for direct intratumoral injection based on the dose level volume of each cohort and cumulative lesion size; according to the investigator's judgement).
• A lesion amenable for additional tumor biopsy.
• Patients with measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
• Life expectancy more than 3 months.
• Willingness to provide mandatory tumor biopsy.
• Male and female patients who agree to use effective contraceptive methods.
• Signed informed consent.

Exclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance score >1.
• Significant and uncontrolled concomitant illness that would adversely affect the patient's participation in the study.
• Any prior organ transplantation.
• History within the last 5 years of an invasive malignancy other than the one treated in this study, with the exception of resected basal or squamous-cell skin cancer or carcinoma, in situ of cervix or other local tumors considered cured by local treatment.
• History of unresolved viral hepatitis; systemic immune suppression including acquired immunodeficiency syndrome (AIDS) related illnesses or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment.
• Prior splenectomy.
• New and progressive brain lesions.
• Poor bone marrow reserve resulting in low blood cell count.
• Poor liver and kidney functions, abnormal coagulation tests.
• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
• Maintenance therapy with prednisolone >7.5 mg/day orally or equivalent during the study.
• Non-resolution of any prior treatment related toxicity to Grade <2, except alopecia, vitiligo, fatigue and hypothyroidism controlled with replacement therapies.
• Moderate to severe immune related adverse event to prior immune-modulating agents within 90 days prior to the first study treatment.
• Central nervous system lymphoma.
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) for patients with lymphoma.
• Autologous HSCT less than 90 days prior to initiation of study intervention.

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