Phase 1/2 Study of Amcenestrant (SAR439859) Single Agent and in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer (AMEERA-1)

Inclusion criteria:

• Participants must be postmenopausal women
• Histological diagnosis of breast adenocarcinoma
• Locally advanced or metastatic disease
• Either primary tumor or any metastatic site to be positive for Estrogen Receptors (ER+) and negative for HER2 (HER2-) receptor
• Participants must have been previously treated with at least 6 months of endocrine therapy for advanced disease:
• Dose Escalation study parts:

        Arm #3 - Part F and Arm #5 - Part J: up to 2 prior lines of either single endocrine therapy
        and/or endocrine-based therapy Arm #4 -H: up to 2 prior lines of either single endocrine
        therapy and/or endocrine-based therapy (exemestane not allowed)
        - Dose Expansion study parts: Arm #2: - Part D: no more than 2 prior lines of advanced
        endocrine therapy for advanced disease are allowed Arm #3, - Part G: patients must have
        received and progressed on the combination of Aromatase Inhibitors (AI) + CDK4/6 inhibitor
        as the first line (1L) treatment for advanced disease Arm #4 - Part I: participants must
        have received and progressed on the combination of Aromatase Inhibitors (AI) +CDK4/6
        Inhibitor as the first line (1L) treatment for advanced disease (exemestane not allowed)
        Arm#5: - Part K: up to 1 prior line of a single endocrine therapy for advanced disease
        Note: Additional patients who relapsed while on previous adjuvant endocrine therapy that
        was initiated ≥24 months ago, or relapsed < 12 months after completion of adjuvant
        endocrine therapy are also allowed for Arms #2, #3, #4, and #5 (Parts C, D, F, G, H, I, J
        and K).
          -  Participants previously treated with chemotherapy for advanced disease: no more than 3
             prior chemotherapeutic regimens in Arm #1 Part A, and no more than 1 prior
             chemotherapeutic regimen in Arms #1, #2, #3, #4, and #5 (Parts B, C, D, F, H and J
             respectively); prior chemotherapy for advanced disease is not allowed in dose
             expansion of Arms #3, #4, and #5 (Part G, I and K respectively).
          -  Measurable lesion
        Exclusion criteria:
          -  Medical history or ongoing gastrointestinal disorders that could affect absorption of
             oral study drugs (including difficulties with swallowing capsules)
          -  Participants with any other cancer (except for adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer or any other cancer from which the
             participant has been disease free for >3 years)
          -  Participants with known brain metastases
          -  Treatment with anticancer agents (including investigational drugs) less than 2 weeks
             before first study treatment starts (less than 4 weeks if the anticancer agents were
             antibodies)
          -  Prior treatment with another selective ER down-regulator (SERD)
          -  Dose Escalation study parts (Parts F, H and J): SERDs are not allowed except for
             fulvestrant which will need a washout of at least 6 weeks prior to the first study
             drug administration
          -  Dose Expansion study parts (Parts G, I and K): prior (last) treatment with any SERD
             including fulvestrant will not be allowed
          -  Inadequate hematological and biochemical lab tests
          -  Participants with Gilbert disease
          -  Treatment with HIV-antiviral, antifungal and antioxidant agents less than 2 weeks
             before study treatment starts
          -  Treatment with strong P450 (CYP) 3A inducers within 2 weeks before first study
             treatment
          -  Treatment with OATP1B1/B3 sensitive substrates and which cannot be replaced
          -  Arm#2 Treatment with strong CYP3A inhibitors within 2 weeks before first study
             treatment starts
          -  More than one prior advanced cyclin-dependent kinase (CDK) 4/6 inhibitor-based therapy
             in Arm #1, Arm #2 (Part C), Arm #3 (Parts F and G), and Arm#4 (Part H).
          -  Arm #2, #3, #4 and #5 (Parts C, D, F, G, H, I, J and K) only: participants with
             concurrent or history of pneumonitis
          -  Arm #3, #4 and #5 (Parts F, G, H, I, J and K) only: prior treatment therapies that
             target the PI3K axis (mTOR inhibitors, AKT inhibitors, PI3K inhibitors)
          -  Arm #3 and #4 (Parts F, G, H and I) only: participants with diabetes mellitus type-I
             or uncontrolled diabetes mellitus type-II: ie, fasting plasma glucose ≥ 140mg/dl (7.7
             mmol/l) or HbA1C > 6.2%
          -  Arm #3 and #4 (Parts F, G, H and I) only: history of severe cutaneous reaction (eg.
             Stevens-Johnson syndrome [SJS], erythema multiforme [EM]), toxic epidermal necrolysis
             (TEN), and drug reaction with eosinophilia and systemic symptoms [DRESS].
          -  Arm #3 (Parts F and G) only: ongoing osteonecrosis of jaw
          -  Arm #4 (Parts H and I) only: any active, untreated or uncontrolled infection (e.g.
             viral, bacterial, fungal etc.)
          -  Arm #4 (Parts H and I) only: participants with active and uncontrolled stomatitis,
             angioedema due to concomitant treatment with ACE inhibitors, impaired wounds
          -  Arm #4 (Parts H and I) only: uncontrolled hypercholesterolemia, hypertriglyceridemia
             and hyperglycemia in non-diabetic participants
          -  Arm #4 (Parts H and I) only: treatment with strong or moderate CYP3A4 inhibitors,
             strong CYP3A4 inducers and/or P-gp inhibitors within 2 weeks before the first study
             treatment administration or 5 elimination half-lives, whichever is the longest
          -  Arm #5 (Parts J and K) only: history or current (controlled/not controlled) venous
             thromboembolism (i.e. deep vein thrombosis (DVT), pulmonary embolism (PE), cerebral
             venous sinus thrombosis (CVST)
        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.