395P - Interim analysis (IA) of the giredestrant (G) + ipatasertib (IPAT) 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

Many pts with ER+ BC experience disease relapse during/after adjuvant endocrine therapy (ET) or develop resistance due to ESR1 mutations. G is a highly potent non-steroidal oral (PO) selective ER antagonist and degrader; IPAT is a potent, PO, AKT inhibitor. We present a 16-week IA of G vs. G + IPAT in MORPHEUS BC (NCT04802759).

Methods

Pts with disease progression on 1–2 lines of ET (including a cyclin-dependent kinase 4/6 inhibitor [CDK4/6i]) for LA/mBC were randomised 1:6 to G (30 mg PO daily [QD]) or G + IPAT (400 mg PO QD; Days 1–21 per 28-day cycle) until disease progression/unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR); other endpoints included progression-free survival, overall survival, clinical benefit rate (CBR), disease control rate, duration of response and pharmacokinetics. Genetic alterations were defined using baseline circulating tumour DNA.

Results

As of 17 May 2022, eight and 24 pts (23 evaluable) were enrolled in the G and G + IPAT arms, respectively; 50% (n = 4)/75% (n = 18) received one prior line and 38% (n = 3)/25% (n = 6) received two prior tx lines for LA/mBC. In the overall population the ORR was 0%/17% (n = 4) and stable disease (SD) was 63% (n = 5)/52% (n = 12) in the G and G + IPAT arms, respectively. In pts with AKT signalling alterations (G = 3; G + IPAT = 10), ORR was 0%/30% (n = 3) and SD was 67% (n = 2)/70% (n = 7). Updated data will be presented including longer follow-up and CBR. Table: 395P

Conclusions

Encouraging activity was seen with G + IPAT in pts with disease progression on 1–2 lines of ET (including a CDK4/6i), especially in pts with AKT signalling alterations. G + IPAT was well tolerated, with no unexpected safety signals.

Clinical trial identification

NCT04802759; 17 March 2021.

Editorial acknowledgement

Research support for third-party writing assistance for this abstract, furnished by Chantel Swart, Ph.D. of Health Interactions, 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

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 Role: AstraZeneca, Celgene, Eisai, F. Hoffmann-La Roche Ltd, Takeda Bixink, Everest Medicine, Daiichi Sankyo, Pfizer, MSD, Novartis . S.J. Luen: 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, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. M. Oliveira: 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 Role: AstraZeneca, Daiichi Sankyo/AstraZeneca, Gilead Sciences, ITeos Therapeutics, Pierre Fabre, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seagen; Financial Interests, Personal, Other, Honoraria: Eisai Europe, Guardant Health, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Seagen; Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, GSK, Immunomedics, Novartis, Puma Biotechnology, F. Hoffmann-La Roche Ltd/Genentech, Inc., Seagen, Zenith Epigenetics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Eisai, Novartis, Pierre Fabre, F. Hoffmann-La Roche Ltd. J. Sohn: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, Sanofi. S. Im: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Hanmi, Lilly, MSD, Novartis, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc.; Financial Interests, Institutional, Research Funding: AstraZeneca, Daewoong Pharmaceutical, Eisai, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc.. S. Wander: 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 Role: Biovica, Eli Lilly, Foundation Medicine Inc., Hologic, Pfizer, Puma Biotechnology, Vercyte ; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Guardant Health, 2ndMD; Financial Interests, Institutional, Research Funding: Genentech, Inc., Eli Lilly, Nuvation Bio, Pfizer, Regor Therapeutics. S.A. Hurvitz: 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, Stocks/Shares: Ideal Implant (I), ROM Tech (I); Financial Interests, Institutional, Research Funding: Ambrx, Amgen, Arvinas, Bayer, Biomarin, Cascadian Therapeutics, Daiichi Sankyo, Dignitana, Genentech, Inc./F. Hoffmann-La Roche Ltd, Gilead Sciences, GSK, Immunomedics, Lilly, Macrogenics, Merrimack, Novartis, OBI Pharma, Pfizer, Phoenix Mole; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly. A. Sonnenblick: 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 Role: AstraZeneca, Eli Lilly, F. Hoffmann-La Roche Ltd, Gilead, MSD, Novartis, Pfizer, Progenetics; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, F. Hoffmann-La Roche Ltd, Novartis, Pfizer, Teva; Financial Interests, Institutional, Research Funding: F. Hoffmann-La Roche Ltd, Novartis; Financial Interests, Personal, Other, Travel, accommodations, expenses: Celgene, F. Hoffmann-La Roche Ltd, Medison, MSD, Neopharm. V. Breton: Non-Financial Interests, Institutional, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. A. Collier: Other, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.. S. Deb, H. Ngo, R. Schwab, C. Shemesh : Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Full or part-time Employment: Genentech, Inc.. J. Zhu: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd Genentech, Inc.; Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd Genentech, Inc.. C. Hernando Melia: Non-Financial Interests, Personal, Other, Research funding: Support for third-party writing assistance from F. Hoffmann-La Roche Ltd: F. Hoffmann-La Roche Ltd.