Abstract 333TiP
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.
Trial design
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.
Clinical trial identification
NCT03284957.
Editorial acknowledgement
Editorial support was provided by Amanda Sheldon, PhD of inScience Communications (Philadelphia, PA, USA), funded by Sanofi.
Legal entity responsible for the study
Sanofi.
Funding
Sanofi.
Disclosure
M. Campone: Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant: Takeda; Financial Interests, Personal and Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Research Grant: Servier; Financial Interests, Personal and Institutional, Research Grant: Sandoz; Financial Interests, Personal and Institutional, Research Grant: Accord; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Lilly. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Radius Health; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Daiichi Pharma/AstraZeneca; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Biothernostics Inc.; Financial Interests, Personal, Advisory Board: Phillips; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Radius Health; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Daiichi Pharma/AstraZeneca. P. Kabos: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Lilly; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Sanofi; Financial Interests, Personal, Research Grant: Radius Health. S. Chandarlapaty: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Paige.ai; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Paige.ai. P. Neven: Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Radius Health; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Roche. V. Boni: Financial Interests, Personal, Other, Honoraria: Loxo; Financial Interests, Personal, Other, Honoraria: IDEAYA Biosciences; Financial Interests, Personal, Advisory Role: OncoArt; Financial Interests, Personal, Advisory Role: Guidepoint Global; Financial Interests, Personal, Speaker’s Bureau: Solti; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Loxo; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: CytomX Therapeutics; Financial Interests, Institutional, Research Grant: Kura Oncology; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Menarini; Financial Interests, Institutional, Research Grant: Synthon; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Zenith Epigenetics; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: BioNTech AG; Financial Interests, Institutional, Research Grant: Boston Biomedical; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Pharmaceuticals Inc; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bayer HealthCare Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: START. S. Lord: Financial Interests, Personal, Full or part-time Employment, Previously employed: Pfizer; Financial Interests, Personal, Stocks/Shares: Mitox Therapeutics; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Research Grant: PATHIOS Therapeutics; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Prosigna; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Travel, accommodation or expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodation or expenses: Roche; Financial Interests, Personal, Other, Travel, accommodation or expenses: Synthon; Financial Interests, Personal, Other, Travel, accommodation or expenses: Piqur Therapeutics; Financial Interests, Personal, Other, Fees for acting on independent data monitoring committee: Shionogi. S. Cartot-Cotton, M. Celanovic, A. Gosselin, V. Pelekanou: Financial Interests, Personal, Full or part-time Employment: Sanofi. H.M. Linden: Other, Personal, Stocks/Shares, An Immediate Family Member: Evolent; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Tolmar; Financial Interests, Institutional, Research Grant: Zionexa; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Zenatalis; Financial Interests, Institutional, Research Grant: Zymeworks.