AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer

Aditya Bardia, Sarat Chandarlapaty, Hannah M. Linden, Gary A. Ulaner, Alice Gosselin, Sylvaine Cartot-Cotton, Patrick Cohen, Séverine Doroumian, Gautier Paux, Marina Celanovic, Vasiliki Pelekanou, Jeffrey E. Ming, Nils Ternès, Monsif Bouaboula, Joon Sang Lee, Anne-Laure Bauchet and Mario Campone ()
Additional contact information
Aditya Bardia: Harvard Medical School
Sarat Chandarlapaty: Memorial Sloan Kettering Cancer Center
Hannah M. Linden: University of Washington Medical Center, Seattle Cancer Care Alliance
Gary A. Ulaner: Hoag Family Cancer Institute
Alice Gosselin: Sanofi
Sylvaine Cartot-Cotton: Sanofi
Patrick Cohen: Sanofi
Séverine Doroumian: Sanofi
Gautier Paux: Sanofi
Marina Celanovic: Sanofi
Vasiliki Pelekanou: Sanofi
Jeffrey E. Ming: Sanofi
Nils Ternès: Sanofi
Monsif Bouaboula: Sanofi
Joon Sang Lee: Sanofi
Anne-Laure Bauchet: Sanofi
Mario Campone: René Gauducheau

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract AMEERA-1 is a Phase 1/2 open-label single-arm study evaluating once-daily (QD) amcenestrant, an orally bioavailable selective estrogen receptor (ER) degrader, in postmenopausal women with ER+/HER2− advanced breast cancer (NCT03284957), who were mostly heavily pretreated (including targeted therapies and fulvestrant). In the dose escalation phase (Part A: n = 16), patients received amcenestrant 20-600 mg QD. Based on absence of dose-limiting toxicities, paired functional 18F-fluoroestradiol positron emission tomography, and pharmacokinetics, 400 mg QD was selected as recommended Phase 2 dose (RP2D) for the dose expansion phase (Part B: n = 49). No Grade ≥3 treatment-related adverse events or clinically significant cardiac/eye toxicities were reported. The Part B primary endpoint, confirmed objective response rate (ORR) was 3/45 at the interim analysis and 5/46 (10.9%) at the final analysis. The overall clinical benefit rate (CBR) was 13/46 (28.3%). CBRs among patients with baseline wild-type and mutated ESR1 were 9/26 (34.6%) and 4/19 (21.1%), respectively. Paired tumor biopsy and cell-free DNA analyses revealed ER inhibition and degradation, and a reduction in detectable ESR1 mutations, including Y537S. In conclusion, amcenestrant at RP2D of 400 mg QD for monotherapy is well-tolerated with no dose-limiting toxicities, and demonstrates preliminary antitumor activity irrespective of baseline ESR1 mutation status.

Date: 2022
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DOI: 10.1038/s41467-022-31668-8

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