212MO - AMEERA-3, a phase II study of amcenestrant (AMC) versus endocrine treatment of physician’s choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC)

Background

AMC (SAR439859), an optimized oral selective ER degrader (SERD), showed encouraging antitumor activity and favorable safety in a phase I/II study of ER+/HER2– aBC pts who progressed after endocrine-based therapy.

Methods

AMEERA-3 (NCT04059484), an open-label phase II randomized study, enrolled postmenopausal women, or premenopausal women or men taking a GnRH agonist, with ER+/HER2− aBC who received ≤ 2 prior lines of ET and ≤ 1 prior chemotherapy or ≤ 1 targeted therapy for aBC. Pts were randomized 1:1 to AMC 400 mg QD (4 x 100 mg capsules) or single agent TPC (fulvestrant, aromatase inhibitor, or tamoxifen) and stratified for the presence of visceral metastasis, prior CDK4/6 inhibitor (i), and ECOG performance status 0 or 1. The primary endpoint was progression-free survival (PFS) assessed by independent central review (ICR). Key secondary endpoints included overall survival (OS) and safety. PFS was compared using a stratified log-rank test at one-sided significance of α = 0.025.

Results

AMEERA-3 randomized 290 pts to AMC (n = 143) or TPC (n = 147). Baseline characteristics were balanced across arms. 79% of pts received prior CDK4/6i for aBC. In the TPC arm, 90% of pts received fulvestrant. AMEERA-3 did not meet its primary objective; PFS per ICR was numerically similar between AMC and TPC (median PFS 3.6 vs 3.7 months; HR = 1.051 [95% CI: 0.789, 1.4]; P = 0.6437). Results for PFS per investigator assessment and in key prespecified subgroups were generally consistent with the primary analysis. OS was numerically similar (data not mature). Common (≥ 5% in either arm) treatment-related adverse events (TRAEs) with AMC vs TPC were mostly Grade 1/2: nausea (14.0% vs 4.1%), vomiting (8.4% vs 1.4%), hot flush (8.4% vs 7.5%), asthenia (7.0% vs 1.4%), fatigue (5.6% vs 6.1%), and injection site pain (0% vs 6.8%); 4.9% vs 0.7% of pts had Grade ≥ 3 TRAEs.

Conclusions

AMC showed numerically similar PFS as TPC in pts with endocrine-resistant ER+/HER2− aBC. The safety profile of AMC was consistent with earlier studies. Clinical development of AMC continues, with a focus on earlier-line breast cancer indications for pts with endocrine-sensitive disease in AMEERA-5 and -6.

Clinical trial identification

NCT04059484.

Editorial acknowledgement

Editorial support was provided by Amanda Sheldon, PhD, CMPP, of inScience Communications (Philadelphia, PA, USA), funded by Sanofi.

Legal entity responsible for the study

Sanofi.

Funding

Sanofi.

Disclosure

S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, SeaGen, Daichii Sankyo, 4D Pharma, Puma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Other, Consultant: Nektar, Nanostring, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol-Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. K. Petrakova: Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Elli Lilly, Roche, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Novartis, AstraZeneca, Elli Lilly, Roche. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre fabre, Orion, Sanofi, Rappta, Cellectis, Isis/servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, AstraZeneca, Orion, Sanofi, Pfizer; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. M. Campone: Financial Interests, Personal, Advisory Role: Amgen, Gilead, Novartis, MSD, Pfizer, Lilly, Pierre Fabre, Sanofi, Seagen, GSK; Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Novartis, Sanofi; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer, Amgen, Novartis. P.A. Kaufman: Financial Interests, Personal, Advisory Role: Polyphor, Roche/Genentech, Lilly, Eisai, Macrogenics, Pfizer, Merck, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly, Polyphor, Macrogenics; Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Other, Honoraria: Lilly, Polyphor, Macrogenics, Eisai; Financial Interests, Institutional, Research Grant: Eisai, Polyphor, Roche/Genentech, Lilly, Novartis, Macrogenics, Pfizer, Sanofi. E. de Kermadec: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi; Financial Interests, Personal, Other, Spouse working in Sanofi Oncology (but cope not related to the trial): Sanofi. Q. Liu: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. P. Cohen: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi. G. Paux: Financial Interests, Personal, Full or part-time Employment: Sanofi; Financial Interests, Personal, Stocks/Shares: Sanofi; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Sanofi. S. Im: Financial Interests, Personal, Research Grant: AstraZeneca, Eisai, Daewoong, Roche, Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Eisai, GSK, MSD, Lilly, Novartis, Roche, Pfizer, Daiichi Sankyo, Hanmi; Financial Interests, Personal, Other: Roche. All other authors have declared no conflicts of interest.