Abstract 355TiP
Background
HR+/HER2– BC is the most common BC subtype, and adjuvant endocrine therapies (ET) are an integral part of its management; however, ∼30% of pts still relapse. Development of ET resistance remains a challenge in HR+/HER2– BC; aberrant PI3K signalling contributes to ET resistance and PIK3CA mutations occur in ∼40% of HR+/HER2– BCs. Current research has led to the development of new targeted therapies, including CDK4/6 inhibitors and PI3K inhibitors (alpelisib). Preclinical models have demonstrated synergy between CDK4/6 inhibitors and PI3K inhibitors, with PI3K inhibitors blocking CDK4/6 inhibitor resistance development. GDC-0077 is a potent, selective PI3Kα inhibitor and a mutant p110α-degrader with anti-tumour activity alone and in combination with ET + P in PIK3CA-mutant preclinical models. An ongoing phase I trial showed that GDC-0077 + P + F could be combined at maximum doses. INAVO120 is a phase III, randomised, double-blind, pbo-controlled study that will assess efficacy and safety of GDC-0077/pbo + P + F in pts with PIK3CA-mutant/HR+/HER2– LA/MBC (NCT04191499).
Trial design
Eligible pts, whose disease progressed during/within 12 months of adjuvant ET completion and who have not received prior systemic therapy for LA/MBC will be randomised 1:1 to GDC-0077 (9 mg orally; QD continuously on a 28-day cycle) + P (125 mg orally; QD, days 1–21 of each 28-day cycle) + F (500 mg intramuscularly every 28 days with a loading dose in Cycle 1) or pbo + P + F. Circulating tumour DNA or tumour tissue must be positive for a PIK3CA mutation. Randomisation will be stratified by visceral disease, primary vs. secondary ET resistance and geographical region. The primary endpoint is investigator-assessed PFS using RECIST v1.1. Secondary endpoints include objective response rate; best overall response; duration of response; clinical benefit rate; overall survival; safety; patient-reported outcomes; and pharmacokinetics. Approximately 400 pts will be enrolled at ∼210 sites globally.
Clinical trial identification
NCT04191499.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Stephen Salem, BSc, 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
N. Turner: Honoraria (self), Advisory/Consultancy: AstraZeneca, Bristol-Myers Squibb, Lilly, Merck Sharpe and Dohme, Novartis, Pfizer, Roche/Genentech, Bicycle Therapeutics, Taiho, Zeno Pharmaceuticals, Repare Therapeutics; Research grant/Funding (institution): AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Merck Sharpe and Dohme, Guardant Health; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. K. Jhaveri: Advisory/Consultancy: Novartis, Pfizer, Genentech, Inc., Lilly Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, ADC Therapeutics, Taiho Oncology, Jounce Therapeutics, AbbVie; Research grant/Funding (self): Pfizer, Genentech, Inc., Novartis, Lilly Pharmaceuticals, AstraZeneca, Immunomedics, Puma Biotechnology, Novita Pharmaceuticals, ADC Therapeutics, Zymeworks, Debio Pharmaceuticals, Clovis Oncology; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. K. Kalinsky: Speaker Bureau/Expert testimony: Lilly; Research grant/Funding (institution): Immunomedics, Novartis, Incyte, Genentech/Roche, Eli Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis Pharmaceuticals, CytomX Therapeutics; Travel/Accommodation/Expenses: Lilly, AstraZeneca; Spouse/Financial dependant, Spouse currently employed: GRAIL; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd; Spouse/Financial dependant, Spouse previously employed: Novartis, Array Biopharma, Pfizer. S. Loibl: Honoraria (self): Chugai; Honoraria (institution): AbbVie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Seattle Genetics, PriME/Medscape, Lilly, Samsung, BMS, Puma, MSD; Advisory/Consultancy: AbbVie, Amgen, AstraZeneca, Celgene, Novartis, Pfizer, Roche, Eirgenix, Lily, Samsung, BMS, Puma; Research grant/Funding (institution): Teva, Vifor, Daiichi-Sankyo, Immunomedics; Licensing/Royalties: EP14153692.0 Immunsignature in TNBC pending; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. S. Loi: Research grant/Funding (institution): Novartis, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology ,Pfizer, Eli Lilly, Seattle Genetics; Non-remunerated activity/ies, not paid: Seattle Genetics, Pfizer, Novartis, BMS, Merck, AstraZeneca, Roche-Genentech; Advisory/Consultancy, paid to institution: Aduro Biotech, Novartis, G1 Therapeutics; Research grant/Funding (institution), support: National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. S-A. Im: Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Eli-Lilly, Hanmi, Novartis, Roche, Pfizer; Research grant/Funding (institution): AstraZeneca, Pfizer, Roche; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. C. Saura: Advisory/Consultancy: AstraZeneca, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genomic Health, Merck, Sharp and Dhome España S.A., Novartis, Odonate Therapeutics, Pfizer, Philips Healthwork, Pierre Fabre, prIME Oncology, Puma, Synthon, Sanofi Aventis; Research grant/Funding (institution): AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, Genentech, Inc., Immunomedics, Macrogenics, Merck, Sharp and Dhome España S.A., Novartis, Pfizer, Piqur Therapeutics, Puma, Roche, Synthon, Zenith PharmaD; Travel/Accommodation/Expenses: AstraZeneca, Celgene, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genomic Health, Merck, Sharp and Dhome España S.A., Novartis, Odonate Therapeutics, Pfizer, Philips Healthwork, Pierre Fabre, prIME Oncology, Puma, Synthon, Sanofi Aventis; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. P. Schmid: Advisory/Consultancy: Pfizer, AstraZeneca, Novartis, Roche, Merck, Boehringer Ingelheim, Bayer, Eisai, Celgene, Puma; Research grant/Funding (institution): Roche, Genentech, Oncogenex, Novartis; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. J.L. Schutzman: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. T. Stout: Full/Part-time employment: Genentech, Inc.; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. G. Lei: Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. K.E. Hutchinson: Shareholder/Stockholder/Stock options: Roche ; Full/Part-time employment: Roche/Genentech; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. E. Thanopoulou: Leadership role: Roche Products Limited; Full/Part-time employment: Roche Products Limited; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd. D. Juric: Advisory/Consultancy: Novartis, Genentech, EMD Serono, Eisai, Ipsen, Syros, Vibliome Therapeutics, Relay Therapeutics, MapKure, Petra Pharma, Silverback Therapeutics; Research grant/Funding (institution): Novartis, Genentech, Eisai, EMD Serono, Pfizer, Syros, Takeda, Amgen, InventisBio, Dizal Pharma, Celgene, Infinity Pharmaceuticals; Non-remunerated activity/ies, Third-party writing assistance: F. Hoffmann-La Roche Ltd.