Phase 1 / 2 Study of SAR439859 Single Agent and in Combination With Palbociclib in Postmenopausal Women With Estrogen Receptor Positive Advanced Breast Cancer

Status: Active

Description

Primary Objectives: Dose Escalation: Part A (SAR439859 monotherapy); Part C (combination of SAR439859 with palbociclib) - To determine the maximum tolerated dose (MTD) and recommended dose (RD) of SAR439859 based on the dose-limiting toxicity (DLT) observance in monotherapy (Part A), and in combination with palbociclib (Part C) Dose Expansion: Part B (SAR439859 monotherapy); Part D (combination of SAR439859 with palbociclib) - To assess antitumor activity by Objective Response Rate (ORR) at the SAR439859 recommended dose in monotherapy (Part B), and in combination with palbociclib (Part D) Secondary Objectives: - Overall safety profile of SAR439859 as monotherapy (Parts A, B), and in combination with palbociclib (Parts C, D) - Pharmacokinetic (PK) profile of SAR439859 as monotherapy (Parts A, B), and of SAR439859 in combination with palbociclib (Parts C, D), and of palbociclib in combination with SAR439859 (Parts C, D) - Antitumor activity of SAR439859 as monotherapy (Part A), and in combination with palbociclib (Part C) as well as the Clinical Benefit Rate (CBR: Complete Response [CR], Partial Response [PR] and Stable Disease [SD] ≥24 weeks) in Parts A, B, C, and D - ORR and CBR (CR, PR and SD ≥24 weeks) according to the estrogen receptor 1 (ESR1) gene mutational status (mutant and wild type) at baseline and in treatment - Time to first tumor response (CR or PR) in Parts B and D - Residual estrogen receptor (ER) availability with [(18)F] Fluoroestradiol Positron Emission Tomography (FES PET) scan (Part A) - To assess potential induction / inhibition effect of SAR439859 on CYP3A (Part B)

Eligibility Criteria

Inclusion Criteria

  • Inclusion criteria: Parts A, B, C and D: - Patients 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 - Patients previously treated for advanced disease: at least 6 months exposure to endocrine therapy, no more than 3 prior chemotherapeutic regimens in Part A, and no more than 1 prior chemotherapeutic regimen in Parts B, C or D (including Antibody Drug Conjugates) - Measurable lesion Part C and D only: - Relapse during or within 12 months after completion of adjuvant hormonal therapy Exclusion criteria: - Medical history or ongoing gastrointestinal disorders that could affect absorption of SAR439859 and/or palbociclib (including difficulties with swallowing capsules) - Patient 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 patient has been disease free for >3 years) - Patients with known brain metastases and endometrial disorders - 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) (except fulvestrant) with a washout of at least 6 weeks prior to the first study drug administration - Inadequate hematological and biochemical lab tests - Patients with Gilbert disease - Treatment with human immunodeficiency virus (HIV)-antiviral, antifungal and antioxidant agents less than 2 weeks before study treatment starts - Treatment with strong and moderate CYP3A inducers within 2 weeks before first study treatment Part A only: - Patients with liver metastases only Part C only: - More than 1 prior therapy with any selective cyclin-dependent kinase (CDK) 4/6 inhibitor Part D only: - Prior therapy with any selective CDK 4/6 inhibitor Part C and D only: - Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment starts - Medical conditions requiring concomitant medications that are metabolized by CYP3A The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Locations & Contacts

Colorado

Aurora
University of Colorado Hospital
Status: Active
Name Not Available

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Temporarily closed to accrual
Name Not Available

South Carolina

Charleston
Medical University of South Carolina
Status: Temporarily closed to accrual
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

Duration of the study, per patient, will include eligibility period (screening period) of up to 4 weeks (28 days), treatment period (at least 1 cycle [28 days] of study treatment), and end of treatment (EOT) visit after the last study treatment administration (i.e. at least 30 days post last treatment or until the patient receives another anticancer therapy, whichever is earlier). The expected enrollment period is approximately 30 months.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Sanofi Aventis

Trial IDs

Primary ID TED14856
Secondary IDs NCI-2017-01882, U1111-1189-4896, 2017-000690-36
Clinicaltrials.gov ID NCT03284957