Abstract 158TiP
Background
Giredestrant (G) is a potent new-generation oral selective estrogen receptor degrader and a full antagonist of estrogen receptor (ER). Preliminary results showed promising clinical activity and benefit rates of G in both metastatic (m) and neo-adjuvant (NA) breast cancer (BC) settings. In the preoperative setting, G showed superiority over anastrazole in achieving a complete cell cycle arrest (CCCA). The first data on the combination of G and abemaciclib (A) showed a good safety profile with a 40% clinical benefit rate in heavily pre-treated patients (pts) with ER+ HER2- mBCs. In the NA setting, the addition of CDK4/6 inhibitors, such as A, to the standard endocrine therapy (ET) enhanced CC control with a significant increase in CCCA rates in the association arm compared with the ET arm. The Neo-Agile trial is a multicentric phase II, window-of-opportunity (WOO)/neoadjuvant study that will evaluate the safety and pharmacodynamics of G in combination with A in ER+ early BC (EBC). The study will also serve to better understand the clinical potential of the A-G combination to move forward with new trials to consolidate this combination in the NA/adjuvant setting of ER+ and HER2- BC.
Trial design
Eligible patients (pts) (post-menopausal women) have a confirmed diagnosis of untreated ER+/HER2- EBC (cT1c–4a–c; cN0-N2a). Pts (#51) will receive A 150 mg twice daily and G once daily for a total of 24 weeks (W) (2 W of WOO phase and 22 W of NA phase) before surgery. After the WOO phase pts will undergo a core biopsy to centrally assess the CCCA. The primary endpoint, CCCA (central Ki67<2.7%) at W2, will be assessed by a blinded independent central review. Secondary outcomes include percent change in Ki67 expression from baseline to W2, ROR score reduction (from baseline to W2 and surgery), clinical and radiologic (magnetic resonance imaging) objective responses, safety, and quality of life assessments. Exploratory endpoints are mechanisms of response and resistance to therapy, the correlation between gut/loco regional microbiome and response to treatment, the correlation between Ki-67% reduction and 18-Fluorothymidine (FLT) uptake reduction and pathological complete response rate (ypT0/is, ypN0) of G plus A.
Clinical trial identification
EudraCT 2023-510153-42-00.
Legal entity responsible for the study
The authors.
Funding
Acknowledgement: OncotechFoundation and CRT (Clinical Research Technology – Salerno) Funding and drug supply: Roche S.p.A e (Funding and drug supply), Eli Lilly Italia S.p.A. (drug supply).
Disclosure
C. von Arx: Financial Interests, Personal, Advisory Board, Receipt of consultation fees: Participation in a company sponsored speaker’s bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Pierre-Fabre, Gentili, Lilly, Novartis, Ipsen; Financial Interests, Personal, Other, Conference Fee and travel grant: Organon; Financial Interests, Personal, Other, Conference fee and travel grant: AAA. R. Caputo: Financial Interests, Invited Speaker: honoraria or speakers' fee from Pierre Fabre, Novartis, Eli Lilly, Roche, AstraZeneca, Daiichi Sankyo, Gilead, Veracyte, Pfizer, MSD and Seagen. V. Di Lauro: Financial Interests, Invited Speaker: honoraria from Novartis, Pfizer, Lilly, Roche, Gentili, Genetic, Exact Sciences, Pierre Fabre and Epionpharma. G. Buono: Financial Interests, Invited Speaker: honoraria or speakers' fee from Pierre Fabre, Novartis, GSK, Eli Lilly, Pfizer, AstraZeneca, Roche, Daiichi Sankyo, Exact Science and Genetic. A. Fabi: Financial Interests, Invited Speaker: advisory boards and/or honoraria for presentations for Roche, Pfizer, Lilly and Celgene. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. F. Puglisi: Financial Interests, Invited Speaker: honoraria for advisory boards, activities as a speaker, travel grants, research grants from Amgen, AstraZeneca, Daiichi Sankyo, Celgene, Eisai, Lilly, Gilead, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda and Viatris; he has received r. P. Vigneri: Financial Interests, Personal and Institutional, Advisory Board: Lilly. L. Del Mastro: Financial Interests, Personal, Invited Speaker, Educational meeting: Novartis, Symposia, Andromeda E20, Vyvamed S.r.l.; Financial Interests, Personal, Invited Speaker, Lecture: Ipsen; Financial Interests, Personal, Advisory Board, Her2+ and TN breast cancer: Roche; Financial Interests, Personal, Invited Speaker, Consultancy for TNBC text: Roche; Financial Interests, Personal, Advisory Board, denosumab: Amgen; Financial Interests, Personal, Advisory Board, Early and metastatic BC: Eli Lilly; Financial Interests, Personal, Invited Speaker, CDK4-6 inhibitors: Eli Lilly; Financial Interests, Personal, Advisory Board, tucatinib: Seagen Int; Financial Interests, Personal, Advisory Board, Oncotype dx: Exact sciences, Havas life; Financial Interests, Personal, Advisory Board, Neratinib: Pierre Fabre; Financial Interests, Personal, Invited Speaker, Internal training: MSD; Financial Interests, Personal, Invited Speaker, Educational meetings: Accademia Nazionale Medicina; Financial Interests, Personal, Invited Speaker, Author for BC text: Pensiero Scientifico Editore; Financial Interests, Personal, Advisory Board, Breast cancer: Uvet; Financial Interests, Personal, Other, Author slide kits and interviews: Think2it; Financial Interests, Personal, Advisory Board, Palbociclib: Pfizer; Financial Interests, Personal, Invited Speaker, Breast cancer: Aristea, Meeting S.r.l.; Financial Interests, Personal, Other, Author slide kits: Forum service; Financial Interests, Personal, Other, Author text about biosimilars: Edizioni Minerva Medica; Financial Interests, Personal, Other, consultant: Kardo S.r.l.; Financial Interests, Personal, Invited Speaker, Breast cancer meetings: Delphi international, Over S.r.l.; Financial Interests, Personal, Invited Speaker: Prex S.r.l., Editree; Financial Interests, Personal, Advisory Board: Uvet, Collage SpA, Daiichi Sankyo, AstraZeneca, Agendia, Gilead, GSK, Eisai, Stemline Menarini; Financial Interests, Personal, Other, Interview: Infomedica S.r.l.; Financial Interests, Personal, Other, Consultant: Sharing progress in cancer care - Switzerland; Financial Interests, Personal, Other, Consultancy: Eli Lilly, Gilead; Financial Interests, Institutional, Funding, National coordinating PI: Roche; Financial Interests, Institutional, Funding, Local PI: AstraZeneca, Roche, Eli Lilly, Daiichi Sankyo, Novella Clinical, Novartis; Financial Interests, Institutional, Invited Speaker: Gilead, Seagen; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Institutional, Product Samples, Genomic Test: FoundationOne. G. Arpino: Financial Interests, Personal and Institutional, Invited Speaker, consultant/advisory board member for Roche, Pfizer, Lilly, MSD, AstraZeneca, Novartis; she has received research support from Roche, Pfizer, Lilly, MSD, AstraZeneca and Novartis (to the institution); declares honoraria from Roche, Pfizer, Lilly, MSD, AstraZeneca and Novartis; has received travel grants from Roche, Pfizer, Lilly, MSD,AstraZeneca and Novartis: consultant/advisory board member for Roche, Pfizer, Lilly, MSD, AstraZeneca, Novartis; she has received research support from Roche, Pfizer, Lilly, MSD, AstraZeneca and Novartis (to the institution); declares honoraria from Roche, Pfizer, Lilly, MSD, Astr. M. De Laurentiis: Financial Interests, Personal and Institutional, Invited Speaker: Roche, Novartis, Lilly, Pierre Fabre, AstraZeneca, MSD, Seagen, Gilead, Daiichi Sankyo, Pfizer and Exact science; he declares honoraria from Roche, Novartis, Lilly, Pierre Fabre, AstraZeneca, MSD, Daiichi Sankyo, Exact science, Gilead, Ipsen, Pfizer, Seagen. All other authors have declared no conflicts of interest.