A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors

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 4 weeks (28 days), a treatment
period of at least 2 cycles (14 days per cycle), 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. Patients who have no disease
progression, and continue to benefit from the study drug(s), will be allowed to continue
treatment beyond the common study end-date at their assigned dose unless the study is
terminated by the Sponsor. The expected enrollment period is approximately 36 months.

Inclusion criteria:

Dose escalation (Part 1A and Part 1B)

- Patients with histologically confirmed, advanced unresectable or metastatic solid
tumor whom in the opinion of the Investigator does not have a suitable alternative
therapy.

Dose expansion (Part 2A)

- Patients with histologically confirmed, advanced unresectable or metastatic melanoma
whom in the opinion of the Investigator does not have a suitable alternative therapy.

- Patients must have failed a prior therapy based on anti-PD-1 or anti-PD-L1 as defined
by disease progression confirmed radiologically within 12 weeks of commencing
treatment without any evidence of a response.

- Patients must have a site of disease amenable to biopsy and be a candidate for tumor
biopsy. Patients must be able to provide mandatory tumor biopsies prior to and during
study treatment.

Dose expansion (Part 2B)

- Patients with histologically confirmed advanced unresectable or metastatic melanoma
who have failed a prior therapy based on anti-PD-1 or anti-PD-L1 or patients with a
specific type of colorectal adenocarcinoma who have progressed after last line of
therapy and have no other alternative approved standard therapy or refuse approved
standard therapy.

Dose expansion (Parts 2A and 2B)

- At least 1 measurable lesion by RECIST v1.1.

All cohorts

- Patient understands and has signed Informed Consent form and is willing and able to
comply with the requirements of the trial.

Exclusion criteria:

- Age <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 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.

- History of known human immunodeficiency virus (HIV), unresolved viral hepatitis.

- 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 that are untreated.

- History of severe, acute or chronic heart diseases.

- History of severe, acute or chronic renal diseases or inadequate renal function.

- Any of the following within 6 months prior to study enrollment: pulmonary embolism,
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 REGN2810.

- 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 2 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 REGN2810 (occasional use of
inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).

- History of pneumonitis or bowel perforation.

- Patients with underlying cancer predisposition syndromes.

- Patients previously treated with idelalisib.

- Receipt of a live vaccine within 30 days of planned start of study medication.

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