Abstract 157TiP
Background
Adjuvant endocrine therapy (ET) for premenopausal women with ER+/HER2- EBC often includes ovarian function suppression (OFS) via a GnRH or LHRH agonist (LHRHa) plus an aromatase inhibitor (AI) or tamoxifen. Younger age is associated with lower rates of ET adherence. New oral selective ER degraders (SERDs) are emerging as potentially useful ETs in the (neo)adjuvant settings. Giredestrant is an efficient and potent SERD and a full antagonist, which translates into better anti-proliferation activity than known SERDs. PREcoopERA aims to determine, in premenopausal women with ER+/HER2- EBC: if giredestrant+LHRHa provides greater anti-proliferative activity than anastrozole+LHRHa; and if giredestrant without LHRHa provides similar (non-inferior) anti-proliferative activity to giredestrant+LHRHa. Results would provide rationale for subsequent (neo)adjuvant clinical trials.
Trial design
PREcoopERA is a randomized, open-label, 3-arm, WOO trial evaluating the anti-proliferative activity and safety of the oral SERD giredestrant +/- LHRHa triptorelin, as compared to the AI anastrozole + triptorelin. Eligible are premenopausal women with untreated ER+/HER2- operable stage I-III EBC, with Ki-67 ≥10%. 220 women will be randomized in 2:2:1 ratio to giredestrant (30 mg/d po for 4 weeks until rebiopsy) + triptorelin (3.75 mg IM on D1); giredestrant alone; or anastrozole (1 mg/d po) + triptorelin. Rebiopsy is planned for D29, either during primary surgery or standalone procedures. The primary endpoint is change in Ki-67 labeling index between pre-treatment diagnostic tumor biopsy and post-treatment rebiopsy. Sample size of 80:80:40 randomized women are planned to test superiority of 4 weeks giredestrant+triptorelin vs anastrozole+triptorelin to reduce Ki-67 (hypothesized percentage changes -80% vs -65%) and to test non-inferiority of 4 weeks giredestrant vs giredesrant+triptorelin (within 10% as non-inferiority margin). The trial was activated on 9 October 2023. The first woman was enrolled on 25 January 2024. The PREcoopERA trial is sponsored and coordinated by ETOP IBCSG PartnersFoundation in collaboration with F. Hoffmann-La Roche Ltd.
Clinical trial identification
NCT05896566.
Legal entity responsible for the study
ETOP IBCSG Partners Foundation.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
E. Munzone: Financial Interests, Personal, Advisory Board: Eisai, Exact Science, MSD Oncology, Daiichi Sankyo/AstraZeneca, Pfizer, Seagen. S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech, Pfizer, Seattle Genetics; Financial Interests, Institutional, Advisory Board, Consultant: Novartis, GSK, Roche Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics; Financial Interests, Institutional, Expert Testimony, COnsultant: PUMA Biotechnologies, BMS; Financial Interests, Institutional, Expert Testimony, consultant: Gilead Therapeutics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly; Financial Interests, Institutional, Funding, Research: Novartis, BMS, Merck, PUMA Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Seattle Genetics, Roche - Genentech; Non-Financial Interests, Advisory Role, Consultant (Non remunerated): Seattle Genetics, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, Roche Genentech; Non-Financial Interests, Advisory Role, consultant (not compensated): Eli Lilly, Pfizer, Gilead Therapeutics. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role, CO-Chair Scientific Committee: International Breast Cancer Study Group. G. Viale: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, MSD Oncology, Pfizer; Financial Interests, Personal, Other, Consulting fees: Agilent; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Advisory Role: Medscape. V. Bjelic-Radisic: Non-Financial Interests, Principal Investigator, PI of the EORTC Follow Up 16-17 studyPI of EORTC QLQ BR Update study: EORTC. P. Karlsson: Financial Interests, Personal, Other, Lecture honoraria: AstraZeneca, Novartis, Seagen; Financial Interests, Personal, Other, Patent co-inventor/IP, not related to the current study: Exact Sciences, Prelude DX. R.M. Connolly: Financial Interests, Personal, Advisory Board, Advisory Board participant-AstraZeneca/Daiichi (HER2 low MBC): AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Advisory Board, AstraZeneca (Olaparib)-Advisory Board participant: AstraZeneca; Financial Interests, Personal, Advisory Board, Gilead (Sacituzumab)-Advisory Board participant: Gilead; Financial Interests, Personal, Advisory Board, Advisory Board participant: Lilly; Financial Interests, Institutional, Funding, Unrestricted Education Grant: Pfizer Global; Financial Interests, Institutional, Research Grant, Research funding to institution for clinical trials: MSD Ireland, Daiichi Sankyo, AstraZeneca; Non-Financial Interests, Advisory Role, Advisory Board Chair: Seagen; Non-Financial Interests, Other, Steering Committee Member-AstraZeneca/Daiichi (HER2 low obs study): AstraZeneca/Daiichi; Non-Financial Interests, Other, Steering Committee member: AICRI, Develop Med -UCD; Non-Financial Interests, Other, Steering Committee Member: Decrescendo; Other, Support for attending St Gallens conference: Novartis; Other, Support for ASCO Conference (virtual): Roche; Other, Support for attending ESMO conference: Novartis; Other, Support for SABCS conference (virtual): Gilead. J.T.L. Ribeiro Mourato: Financial Interests, Personal, Advisory Role: Gilead Sciences, Inc., AstraZeneca, MSD; Financial Interests, Personal, Other, Travel, accommodations and expenses: Gilead Sciences, Inc., Novartis, MSD, Roche; Financial Interests, Personal, Speaker’s Bureau: Gilead Sciences, Inc., MSD. M.M. Regan: Financial Interests, Personal, Advisory Board, Also invited speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Includes consulting: Tolmar Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca, Tersera Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Bayer; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial supported by company: Novartis; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported by company: Pfizer, Ipsen, TerSera; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial drug supply from company: Roche; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported or drug supply from company: AstraZeneca; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials with funding from company: Debiopharm; Financial Interests, Institutional, Funding, IBCSG translational research collaboration: Biotheranostics; Non-Financial Interests, Advisory Role: Bristol Myers Squibb. P. Dubsky: Financial Interests, Institutional, Other, Advisory and Travel support: Roche; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Institutional, Other, Advisory,Travel support, invited speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Grants to ABCSG: Cepheid/Danaher; Financial Interests, Institutional, Invited Speaker, Grant to ABCSG: Oncomark; Non-Financial Interests, Officer, Scientific Committee: IBCSG/ETOP; Non-Financial Interests, Principal Investigator, Co PI: IBCSG Pre-Coopera Trial; Other, Founder of a local therapy network: Toolbox Lucerne. All other authors have declared no conflicts of interest.