273P - A preoperative window-of-opportunity (WOO) study of imlunestrant in ER+, HER2- early breast cancer (EBC): Final analysis from EMBER-2

Background

Imlunestrant is an investigational, next-generation, oral SERD designed to deliver continuous ER target inhibition, including in ESR1-mutant BC. Imlunestrant monotherapy demonstrated favourable safety, pharmacokinetics, and preliminary efficacy in patients (pts) with heavily pre-treated ER+ advanced BC (Jhaveri ASCO 2022). We present final pharmacodynamic (PD) biomarker data from the preoperative EMBER-2 WOO study (NCT04647487), including the expanded data at the 200 mg dose level, evaluating imlunestrant in ER+, HER2- EBC.

Methods

Post-menopausal women with stage I–III operable ER+, HER2- untreated EBC ≥1 cm were enrolled to imlunestrant 200, 400 (RP2D), or 800 mg once daily for approximately two weeks up to the surgery date. Pre- and on-treatment tumor samples were compared for changes in PD biomarkers. Primary endpoint was change in ER expression by IHC. Secondary endpoints were change in progesterone receptor (PR) expression and Ki-67, safety, and tolerability.

Results

Seventy-five pts were evaluable for ER expression (200 mg: n = 22; 400 mg: n = 27; 800 mg: n = 26). Baseline characteristics were similar across cohorts, with a median age of 64 years, 69% invasive ductal carcinoma, 30% invasive lobular carcinoma, 1% other, 55% stage I, 40% stage II and 5% stage III. Among evaluable pts, relative reduction in PD biomarkers after a median of 16 days of treatment are presented in the table. There was no significant difference in PD biomarker modulation between imlunestrant doses or tumor histology. Imlunestrant was well tolerated. Table: 273P

Reduction in PD biomarkers from baseline and safety

N = number of biomarker evaluable pts; n = number of pts in category; GMPC = geometric mean percent change.

Conclusions

Imlunestrant demonstrated evidence of consistent and robust target engagement across all evaluated doses and was well tolerated in an EBC population, supporting adjuvant development in the EMBER-4 study.

Clinical trial identification

NCT04647487.

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

P. Neven: Financial Interests, Institutional, Speaker, Consultant, Advisor: AstraZeneca; Eli Lilly and Company; Hoffman/La Roche; Novartis; Pfizer; Pierre Fabre; Radius Health; Roche; Teva.; Financial Interests, Institutional, Other, Travel and accommodation expenses: Eli Lilly and Company; Pfizer; Roche . M.J. Vidal Losada: Financial Interests, Personal, Advisory Board: Novartis/Pfizer, Roche, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis/Pfizer, Roche/Genentech, AstraZeneca/Daiichi Sankyo, Gilead Sciences; Financial Interests, Personal, Other, Travel, Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Gilead Sciences. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: TRIO; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. 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, Contracted Research: Eli Lilly and Company; Macrogenics; Polyphor; Sanofi ; Financial Interests, Personal, Other, Travel and accommodation expenses: Eli Lilly and Company; Polyphor; Seagen. N. Harbeck: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; AstraZeneca; Daiichi Sankyo; Eli Lilly and Company; Exact Sciences; MSD; Novartis; Pfizer; Pierre Fabre; Roche; Sandoz; Seagen; Financial Interests, Institutional, Research Funding: Roche; Financial Interests, Personal, Stocks or ownership: WSG. K. Hunt: Financial Interests, Personal, Speaker, Consultant, Advisor: Armada Health; AstraZeneca; Merck ; Financial Interests, Institutional, Research Funding: Cairn Surgical; Eli Lilly and Company; Lumicell. S.A. Carter: Financial Interests, Personal, Other, Honoraria: Mena Hereditary Conference; Perimeter. F.C. Bidard: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Rain Oncology; Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Novartis, AstraZeneca, Sanofi, Rain Oncology, GE Healthcare, SAGA Diagnostics, Caris, Daiichi Sankyo, Gilead, Inatherys; Financial Interests, Institutional, Invited Speaker: Pfizer, Sanofi; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: Prolynx, Saga Diagnostics, Seagen, Merck KGaA; Financial Interests, Personal and Institutional, Steering Committee Member: AstraZeneca, Lilly. P. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v.. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly; Financial Interests, Personal, Invited Speaker: Synthon, Amgen; Financial Interests, Institutional, Research Grant: Roche. D. Wheatley: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Gilead; Novartis; Roche. 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 R. Ismail-Khan, C. Karacsonyi, S.T. Estrem, U. Ozbek : Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks or ownership: Eli Lilly and Company. E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. All other authors have declared no conflicts of interest.