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A Phase 1/2 Study for the Safety, Efficacy, Pharmacokinetic and Pharmacodynamics Evaluation of Amcenestrant (SAR439859), Administered Orally as Monotherapy, Then in Combination With Other Anti-cancer Therapies in Postmenopausal Women With Estrogen Receptor-positive Advanced Breast Cancer
Primary Objectives: Dose Escalation: * To assess the incidence rate of dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) as well as the recommended dose (RD) of amcenestrant administered as monotherapy and in combination with palbociclib * To assess the incidence rate of DLT and determine the RD of everolimus or abemaciclib in combination with the selected amcenestrant dose for the combination therapy Safety Run-In: \- To confirm the RD of amcenestrant in combination with alpelisib Dose Expansion: * Antitumor activity using objective response rate (ORR) * Overall safety profile of amcenestrant administered in combination with palbociclib, alpelisib, everolimus, and abemaciclib Secondary Objectives: * Overall safety profile of amcenestrant monotherapy and in combination * Pharmacokinetic (PK) profile of amcenestrant administered as monotherapy or in combination and PK profile of palbociclib, alpelisib, everolimus and abemaciclib * Antitumor activity using ORR, the clinical benefit rate (CBR) and progression free survival (PFS) * Time to first tumor response * Residual ER availability with positron emission tomography (PET) scan \[(18)F\] fluoroestradiol (18F-FES) uptake with increasing doses of amcenestrant * Food effect on PK of amcenestrant * Potential induction/inhibition effect of amcenestrant on cytochrome P450 (CYP) 3A using 4b-OH cholesterol
Duration of the study, per participant, 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 at least 22 to 30 days (or until the participant receives another anticancer therapy, whichever is earlier) following the last study treatment administration. The expected enrollment period is approximately 60 months.
Age
18 - No limit years
Sex
FEMALE
Healthy Volunteers
No
University of Colorado - Anschutz Medical Campus- Site Number : 8400005
Aurora, Colorado, United States
Massachusetts General Hospital- Site Number : 8400002
Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center - New York - York Avenue- Site Number : 8400003
New York, New York, United States
Fred Hutchinson Cancer Center- Site Number : 8400001
Seattle, Washington, United States
Investigational Site Number : 0560001
Leuven, Belgium
Investigational Site Number : 1240004
Edmonton, Alberta, Canada
Investigational Site Number : 1240003
Vancouver, British Columbia, Canada
Investigational Site Number : 1240002
Toronto, Ontario, Canada
Investigational Site Number : 2030002
Brno, Czechia
Investigational Site Number : 2030001
Prague, Czechia
Start Date
September 20, 2017
Primary Completion Date
November 8, 2024
Completion Date
November 8, 2024
Last Updated
November 24, 2025
136
ACTUAL participants
Amcenestrant
DRUG
Palbociclib
DRUG
Alpelisib
DRUG
Everolimus
DRUG
Abemaciclib
DRUG
Lead Sponsor
Sanofi
NCT04704661
NCT05245812
Data Source & Attribution
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