Breast Cancer Metastatic
Conditions
Interventions
Amcenestrant arm:
- Drug: Amcenestrant (SAR439859)
- - Pharmaceutical form: Capsule Route of administration: Oral
Physician Choice Endocrine Monotherapy arm:
- Drug: Fulvestrant
- - Pharmaceutica
Sponsors
Sanofi K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 years or older. - Histological or cytological diagnosis of adenocarcinoma of the breast. - Locally advanced not amenable to radiation therapy or surgery in a curative intent, and/or metastatic disease. - Estrogen receptor (ER) positive status. - Human epidermal growth factor receptor 2 (HER2) negative status. - Participants must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease. - In the main study, a prior treatment with a CDK 4/6 inhibitor is mandatory if this treatment is approved and can be reimbursed for this participant. The percentage of participants without previous CDK 4/6 inhibitor will be capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6 inhibitor will not be mandatory, and there will be no limitation to the number of participants naive to CDK4/6 inhibitor. - Participants must present a secondary endocrine resistance to endocrine therapy defined as: progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy. - Male or Female.
Exclusion criteria
Exclusion criteria: - Eastern Cooperative Oncology Group performance status >=2. - Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant. Participants unable to swallow normally and to take capsules. - Participant with any other cancer. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant has been disease free for greater than 3 years are allowed. - Severe uncontrolled systemic disease at screening . - Participants with known brain metastases that are untreated, symptomatic or require therapy to control symptoms. - Prior treatment with mammalian target of rapamycin inhibitors or any other selective estrogen receptor degrader (SERD) compound, except fulvestrant if stopped for at least 3 months before randomization. - Treatment with drugs that have the potential to inhibit Uridine'5 Diphospho-Glucuronosyl Transferase (UGT) less than 2 weeks before randomization. - Treatment with strong Cytochrome P450 (CYP)3A inducers within 2 weeks before randomization. - Ongoing treatment with drugs that are sensitive substrate of organic anion transporting polypeptide 1B1/B3 ((OATP1B1/B3) (asunaprevir, atorvastatin, bosentan, danoprevir, fexofenadine, glyburide, nateglinide, pitavastatin, pravastatin, replaglinide, rosuvastatin, and simvastatin acid). - Treatment with anticancer agents (including investigational drugs) less than 3 weeks before randomization. - Inadequate hematological, coagulation, renal and liver functions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression Free Survival (PFS) [Time Frame: Up to 18 months after the first randomized participant] PFS is defined as the time interval from the date of randomization to the date of documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall Survival (OS) [Time Frame: Up to 64 months after the first randomized participant] OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause). 2. Objective Response Rate (ORR) [Time Frame: Up to 18 months after the first randomized participant] ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), as best overall response (BOR) determined by RECIST 1.1 from the date of randomization to the date of end of treatment. 3. Disease Control Rate (DCR) [Time Frame: Up to 18 months after the first randomized participant] DCR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD as BOR determined by RECIST 1.1 from the date of randomization to the date of end of treatment. 4. Clinical Benefit Rate (CBR) [Time Frame: Up to 18 months after the first randomized participant] CBR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) or Non-CR/Non-PD for at least 24 weeks determined by RECIST 1.1 from the date of randomization to the date of end of treatment. 5. Duration of Response (DOR) [Time Frame: Up to 18 months after the first randomized participant] DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by objective radiographic disease assessment per RECIST 1.1 or death from any cause, whichever occurs first. 6. PFS according to (ESR1) mutation status [Time Frame: Up to 18 months after the first randomized participant] PFS as per the estrogen receptor 1 (ESR1) mutation status determined at study entry. 7. Assessments of the Pharmacokinetic (PK) parameter of amcenestrant: Plasma Concentrations [Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of Cycles 3, 4 and 6 (each cycle is 28 days)] Amcenestrant plasma concentrations. 8. Patient Reported Outcome (PRO) - health-related qu | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Greece, Israel, Italy, Japan, Latvia, Mexico, Poland, Puerto Rico, Republic of Korea, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed