383MO - Imlunestrant with or without everolimus or alpelisib, in ER+, HER2- advanced breast cancer (aBC): Results from the phase Ia/b EMBER study

Background

Imlunestrant is an investigational, next-generation, oral SERD designed to deliver continuous ER target inhibition, including in ESR1-mutant BC. In the first-in-human phase 1a/b EMBER study, imlunestrant demonstrated favorable safety, pharmacokinetics (PK), and clinical benefit rate when administered as monotherapy (Jhaveri ASCO 2022) or with abemaciclib (Jhaveri SABCS 2022). We present the first clinical data of imlunestrant with everolimus or alpelisib and updated imlunestrant monotherapy data from the EMBER study (NCT04188548).

Methods

Patients (pts) received imlunestrant alone as part of the phase 1a (escalation) or 1b (expansion), or with everolimus or alpelisib in 1b. Key phase 1b eligibility included ER+, HER2- aBC, prior endocrine therapy (ET) sensitivity, ≤2 prior therapies, and a PIK3CA mutation (alpelisib arm only). Assignment to phase 1b treatment arms was made by investigators. Men and premenopausal women received GnRH agonist. Key endpoints included RP2D, safety, PK, ORR (complete response [CR] plus partial response [PR]) and CBR (CR or PR, or stable disease ≥24 weeks) per RECIST v1.1.

Results

As of 6 Oct 2022, 114 pts received imlunestrant monotherapy, 42 pts received imlunestrant + everolimus, and 21 pts received imlunestrant + alpelisib. Baseline characteristics were similar across combination cohorts; 46% pts had visceral disease and 46% had an ESR1 mutation at baseline. Median number of prior aBC therapies in combination cohorts was: 1 (range 1-2); including prior ET (100%), CDK4/6i (100%), fulvestrant (35%) and chemo (17%). No cardiac or ocular toxicity was seen. Safety and preliminary efficacy are presented (Table). Table: 383MO

Safety and preliminary efficacy

AEs = adverse events.

Conclusions

Imlunestrant alone or in combination with everolimus or alpelisib demonstrated robust efficacy in pts with pre-treated ER+, HER-2 aBC. Toxicities were consistent with the known safety profile of both alpelisib and everolimus.

Clinical trial identification

NCT04188548.

Editorial acknowledgement

John Hurley, Eli Lilly and Company, provided editorial assistance in the writing of this abstract.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

K. Jhaveri: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie; AstraZeneca; Biotheranostics; Blueprint Medicine; BMS, Daiichi Sankyo; Genetech/Roche; Intellisphere; Jounce Therapeutics; Eli Lilly and Company; Novartis; Pfizer; Seattle Genetics; Sanofi; Sun Pharma; Synthon; Taiho Oncology; Financial Interests, Institutional, Research Funding: ADC Therapeutics; AstraZeneca; Clovis Oncology; Debiopharm; Eli Lilly and Company; Genetech Inc.; Gilead; Immunomedics; Merck; Novartis; Novita Pharmaceuticals; Pfizer; Puma Biotechnology; Zymeworks; Financial Interests, Personal, Other, Travel and accommodation expenses: AstraZeneca; Intellisphere; Jounce Therapeutics; Pfizer; Taiho Pharmaceutical. R. Jeselsohn: Financial Interests, Personal, Advisory Role: GE Health; Carrick therapeutics; Financial Interests, Institutional, Research Funding: Eli Lilly and Company; Pfizer. C.X. Ma: Financial Interests, Personal, Speaker, Consultant, Advisor: Agendia; AstraZeneca; Biovica; Inivata; Natera; Novartis; Olaris; Puma Biotechnology; Sanofi; Financial Interests, Institutional, Research Funding: Pfizer; Puma Biotechnology. E. Lim: Financial Interests, Institutional, Advisory Board: Gilead, Novartis, Pfizer, Roche, AstraZeneca, MSD, Lilly; Financial Interests, Institutional, Invited Speaker: Roche, Gilead, Novartis, Lilly, AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer, Novartis; Financial Interests, Institutional, Steering Committee Member: Roche, Lilly, AstraZeneca; Financial Interests, Institutional, Local PI: Novartis, Gilead; Non-Financial Interests, Leadership Role, Scientific Advisory Committee: Breast Cancer Trials Australia; Non-Financial Interests, Leadership Role, Principal Cancer Theme Lead, Faculty of Medicine: University of New South Wales; Non-Financial Interests, Leadership Role, Faculty: Garvan Institute of Medical Research; Non-Financial Interests, Leadership Role, Director Cancer Research: St Vincent's Hospital Sydeny. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boeringer Ingerheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, SeaGen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics K. Harnden: Financial Interests, Personal, Speaker, Consultant, Advisor: Daiichi Sankyo; Merck; SeaGen; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Daiichi Sankyo; Merck; SeaGen. S. Im: Financial Interests, Personal, Advisory Board, no payment: AstraZeneca, Novartis, Eisai, Roche, Hanmi, Pfizer, Lilly, MSD, GSK, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Bertis; Financial Interests, Personal, Advisory Board: Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Pfizer, Roche, Eisai, Dae Woong; Financial Interests, Institutional, Local PI, Clinical Trial Budget: AstraZeneca, Hanmi, Novartis, Roche, Pfizer, Daiichi Sankyo, MSD, Lilly; Financial Interests, Institutional, Coordinating PI, Clinical Trial Budget: Eisai; Financial Interests, Institutional, Research Grant, Clinical Trial Budget: Boryung Pharm. T. Beck: Financial Interests, Institutional, Local PI: Lilly, AZ, Novartis, DSI, AbbVie, Pfizer, johnson and Johnson, BMS, Merck, EMD Serono, Tesaro, Mersano, ascentage pharma, Gritstone, Gilead. S. Sammons: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Daiichi Sankyo; Eli Lilly and Company; Foundation Medicine; Novartis; Pfizer; Seagen; Sermonix Pharmaceuticals; Financial Interests, Institutional, Research Funding: AstraZeneca/MedImmune; Eli Lilly and Company; Seagen, Sermonix Pharmaceuticals. M. Bhave: Financial Interests, Personal, Speaker, Consultant, Advisor: Daiichi Sankyo; Merck; Pfizer. P.A. Kaufman: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Eisai; Eli Lilly and Company; H3 BioMedicine; Pfizer; Polyphor; Roche/Genetech; Sanofi; Seagen; Financial Interests, Personal, Stocks or ownership: Amgen; Financial Interests, Institutional, Research Funding: AstraZeneca; Eisai; Macrogenics; Sanofi; Seagen; Financial Interests, Personal, Other, Travel and accommodation expenses: Eli Lilly and Company; Polyphor; Seagen. C. Saura Manich: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F. Hoffmann - La Roche Ltd, Gilead, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Piere Fabre, PintPharma, Puma, Roche Farma, Sanofi-Aventis, SeaGen, Zymeworks, Genentech, Innoup, Millenium, Pharmalex Spain SLU; Financial Interests, Personal, Other, SC: Byondis B.V., Glaxo, Macrogenics, Menarini, Merus, Synthon Biopharpaceuticals; Financial Interests, Institutional, Research Grant: AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Cytomx Therapeutics, Daiichi Sankyo, Eli Lilly and Company, F. Hoffmann-La RocheLtd, Genentech, GSK, Immunomedics, Innoup Farma, Macrogenics, Menarini Ricerche, Merus, Novartis, Pfizer, Puma, Roche, Sanofi-Aventis, Seattle Genetics; Financial Interests, Institutional, Coordinating PI: Byondis B.V.; Non-Financial Interests, Member: Spanish Society of Medical Oncology (SEOM), American Society for Clinical Oncology (ASCO), Geicam (Spanish Breast Cancer Research Group), European Society for Medical Oncology (ESMO), Sinology Society of the Official College of Physicians of Barcelona (COMB); Non-Financial Interests, Member, Junta Directiva y Comité Científico: SOLTI group (Academic research group in breast cancer). T. Meniawy: Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca/MedImmune; Bristol Myers Squibb; GSK; Novartis; Financial Interests, Institutional, Research Funding: AstraZeneca/MedImmune; Bayer; BeiGene; Bristol Myers Squibb; Incyte; Merck Serono; Regeneron; Roche/Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb. F. Bacchion, R. Ismail-Khan, Y. Li, S.T. Estrem, B. Nguyen: Financial Interests, Personal, Stocks or ownership: Eli Lilly and Company; Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. All other authors have declared no conflicts of interest.