365P - Interim analysis (IA) of the giredestrant (G) + samuraciclib (SAMURA) arm in MORPHEUS breast cancer (BC): A phase I/II study of G treatment (tx) combinations in patients (pts) with oestrogen receptor-positive (ER+), HER2-negative, locally advanced/metastatic BC (LA/mBC)

Background

Finding effective combinations for ER+ mBC after progression on endocrine therapy (ET) + a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a challenge. Targeting CDK7 (a cell cycle regulator) may overcome CDK4/6i-resistance. SAMURA is a selective CDK7i; G is a highly potent, non-steroidal, oral (PO), selective ER antagonist and degrader that is well tolerated and achieves robust ER occupancy. We present a 24-week IA of the G + SAMURA arm in MORPHEUS BC (NCT04802759).

Methods

Eligible pts with disease progression on 1–2 lines of ET (+ CDK4/6i) for LA/mBC were randomised to receive G (30 mg PO daily [QD]) or G + SAMURA (360 mg PO QD) until disease progression/unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR). SAMURA dose decreases to 240 mg and 120 mg were allowed. Gastrointestinal prophylaxis was recommended. Circulating tumour DNA was used to define genetic alterations.

Results

As of 16 October 2023, 18 and 15 pts were enrolled in the G and G + SAMURA arms, respectively; all had ECOG PS 0–1, 66.7% and 33.3% had prior fulvestrant and 72.2% and 46.7% (capped at 7 pts in the G + SAMURA arm) had liver metastasis at enrolment. Safety data are shown in the table; one pt discontinued treatment due to a tx-related adverse event (TRAE; embolism; G + SAMURA arm). In the G and G + SAMURA arms, confirmed ORR was 5.6% vs. 6.7% (both n = 1; partial responses), stable disease was seen in 50.0% (n = 9) and 53.3% (n = 8) of pts and clinical benefit rate was 38.9% vs. 46.7%. Progression-free survival data were immature at data cutoff. No clinically relevant drug–drug interactions were seen between G and SAMURA.

Conclusions

Safety of G + SAMURA was aligned with the individual safety profile of each drug, with no overlapping toxicities or new safety signals. Updated data, including efficacy and biomarkers, will be presented.

Clinical trial identification

NCT04802759.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Brian Law, PhD, of Nucleus Global, an Inizio company, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Cureo Science, Daiichi Sankyo / AstraZeneca, Gilead, Lilly, MSD, Pfizer, Relay Therapeutics, Roche, Seagen, iOne, iTEOS; Financial Interests, Personal, Invited Speaker: AstraZeneca, Eisai, Gilead, Lilly, Medscape, Pfizer, Roche, Seagen, MSD, Novartis; Financial Interests, Personal, Other, Educational activity: Libbs; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Local PI: AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, GSK, Gilead, Pfizer, Roche, Seattle Genetics, Zenith Epigenetics, Immutep; Financial Interests, Personal, Steering Committee Member: AstraZeneca; Financial Interests, Steering Committee Member: Roche; Non-Financial Interests, Member of Board of Directors, President elected 2023-2027: SOLTI Breast Cancer Research; Other, Travel Grant: AstraZeneca, Eisai, Gilead, Pierre Fabre. M. Gion Cortes: Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Novartis; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Full or part-time Employment: Medsir. K.H. Jung: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Board: AstraZeneca, Celgene, Eisai, F. Hoffmann-La Roche Ltd, Takeda, Bixink, Everest Medicine, Daiichi Sankyo, Pfizer, MSD, Novartis, Gilead Sciences. B. bermejo: Financial Interests, Personal, Other, Advisory role/Speaker's Bureau: AstraZeneca, MSD, Pfizer, Novartis, Gilead, Daichii Sankyo, Lilly; Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd. S.A. Hurvitz: Financial Interests, Personal, Invited Speaker: Clinical Care Options, axis medical, cancer expert now, ICHE, MJH Associates, PER, Primo, Projects in Knowledge, Prova Education, Research to Practice, Ultimate Medical Academy, Vaniam, WebMD, Peer Education, PrecisCA, Peer Voice, Curio, Reach MD/MedIQ, Imedex, MD Outlook, Prime Oncology, Reach MD, OncLive; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Personal, Royalties, author medical book: McGraw; Financial Interests, Personal, Royalties: Elsevier, Springer, Sage, Wolters Kluwer, Wiley; Financial Interests, Institutional, Local PI: Ambrx, AstraZeneca, Arvinas, Genentech/Roche, Gilead, GSK, Immunomedics, Eli Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, PUMA, Radius, sanofi, Seattle Genetics, Dignitana, Zymeworks, Phoenix Molecular Designs, Ltd, cytomx, Dantari, G1 Therapeutics, Greenwich Life Sciences, Loxo Oncology, orinove, Orum; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, Celcuity; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Steering Committee Member: Greenwich Life Sciences, Orum; Non-Financial Interests, Advisory Role: Daiichi Sankyo, Novartis, Ambrx, 4DPharma, Dantari, Macrogenics, Lilly, Artios, Roche, Pyxis, Amgen, Pieris, Arvinas, Immunomedics/Gilead, Briacell, Jazz Pharmaceuticals, Boehringer Ingelheim, Stemline/Menarini; Non-Financial Interests, Principal Investigator: Daiichi Sankyo, Genentech, Seattle Genetics; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, speaker: National Breast Cancer Coalition; Non-Financial Interests, Member, site representative for breast cancer guidelines: National Comprehensive Cancer Network. 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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. E. Gal-Yam: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Funding: F. 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