Abstract OT2-11-03: AMEERA-1 : Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with alpelisib in postmenopausal women with ER+/human epidermal growth factor receptor 2-negative (HER2-)PIK3CA-mutated advanced breast cancer
Authors: Campone Mario , Bardia Aditya , Kabos Peter , Chandarlapaty Sarat , Neven Patrick , Boni Valentina , Lord Simon , Cartot-Cotton Sylvaine , Celanovic Marina , Gosselin Alice , Pelekanou Vasiliki , Linden Hannah M 
Published: March 2022

Abstract
Background Amcenestrant is an optimized oral SERD with potent dual activity of ER antagonism and degradation resulting in inhibition of ER signaling. Amcenestrant monotherapy or combination with palbociclib showed antitumor activity and a favorable safety profile in postmenopausal women with heavily pretreated ER+/HER2- mBC. PIK3CA mutations are associated with endocrine resistance in ER+/HER2- patients (pts). Published data support the addition of the PI3Kα inhibitor alpelisib to SERD therapy for these pts. Methods AMEERA-1 (NCT03284957) is an open-label, non-comparative, dose escalation and dose expansion Phase 1/2 study of amcenestrant as monotherapy, then in combination with other anti-cancer targeted therapies. Parts F and G investigate safety run-in and dose expansion, respectively, of amcenestrant in combination with alpelisib. Postmenopausal women with ER+/HER2- advanced breast cancer, PIK3CA mutated in tumor tissue or cfDNA, ECOG performance status 0-1, and ≥ 6 months prior endocrine therapy are eligible. Pts must have progressed on an aromatase inhibitor plus CDK4/6 inhibitor as first-line therapy for advanced disease. Part F allows ≤ 1 prior chemotherapy for advanced disease; no prior chemotherapy is allowed in Part G. Exclusion criteria in Parts F and G include prior drugs targeting the PI3K axis, type 1 diabetes, uncontrolled type 2 diabetes, history of severe cutaneous reactions, and ongoing osteonecrosis of the jaw. Part F assesses dose-limiting toxicities and pharmacokinetics (PK) of a standard dose of amcenestrant plus the approved dose of alpelisib (300 mg once daily). Additional amcenestrant doses or a lower dose of alpelisib may be explored based on safety and PK. The primary objective in Part F is to confirm the recommended phase 2 dose (RP2D) of amcenestrant in combination with alpelisib, based on safety. In Part G, approximately 34 pts will be treated at the RP2D, the primary endpoint being safety and tolerability. Secondary endpoints include PK and antitumor activity. This study is currently recruiting participants. This abstract was previously submitted to the 2021 European Society for Medical Oncology Annual Congress. Funding: Sanofi.
Citation Format: Mario Campone, Aditya Bardia, Peter Kabos, Sarat Chandarlapaty, Patrick Neven, Valentina Boni, Simon Lord, Sylvaine Cartot-Cotton, Marina Celanovic, Alice Gosselin, Vasiliki Pelekanou, Hannah M Linden. AMEERA-1 : Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with alpelisib in postmenopausal women with ER+/human epidermal growth factor receptor 2-negative (HER2-)PIK3CA-mutated advanced breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-11-03.