Abstract 336TiP
Background
Ipatasertib is a potent and selective small-molecule inhibitor of all three isoforms of the serine/threonine kinase AKT. Its beneficial use as a single-agent or in combination with chemotherapeutic, hormonal, or targeted agents for patients (pts) with metastatic breast cancer is supported by in vivo results. Pathfinder is evaluating the safety, tolerability, and preliminary efficacy of ipatasertib in combination with non-taxane chemotherapy agents in taxane-pretreated unresectable advanced TNBC.
Trial design
This is a multicenter, open-label, non-comparative, phase IIa trial with a safety run-in. Main selection criteria include: (a) Female pts with taxane-pretreated unresectable locally advanced or metastatic TNBC amenable to biopsy; (b) At least 1 and up to 2 prior chemotherapeutic regimens in metastatic setting; (c) No prior treatment with PI3K, mTOR, and/or AKT inhibitors; (d) Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A total of 54 evaluable pts (a maximum of 18 pts per arm) will be assigned to one of the following arms according to prior treatments and slots availability: ipatasertib administered orally once a day on days 1-14 of each 21-day cycle, plus either capecitabine administered orally twice a day for 14 days every 21-day cycle (Arm A), eribulin administered intravenously on days 1 and 8 every 21-day cycle (Arm B), or carboplatin on day 1 plus gemcitabine administered intravenously on days 1 and 8 every 21-day cycle (Arm C). Primary endpoint is the incidence of adverse events as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary endpoints include progression-free survival, time to response, objective response rate, duration of response, clinical benefit rate, overall survival, and depth of response. Exploratory objectives encompass the efficacy in the subset of pts with PIK3CA/AKT1/PTEN-altered tumors; predictive or prognostic biomarkers associated with pts baseline clinical features or response to treatment; and mechanisms of resistance to study treatments. This is a pilot study and the analysis will be focused on descriptive statistics and estimation.
Clinical trial identification
NCT04464174.
Editorial acknowledgement
Legal entity responsible for the study
MedSIR.
Funding
Roche.
Disclosure
A. Llombart Cussac: Financial Interests, Personal, Project Lead: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Financial Interests, Personal, Stocks/Shares: MedSIR, Initia-Research; Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, MSD; Financial Interests, Institutional, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, Agendia; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Lilly, Novartis, Pfizer, AstraZeneca. J. Soberino: Financial Interests, Personal, Speaker’s Bureau: MSD, Roche; Financial Interests, Institutional, Research Grant: MSD, Sanofi. M. Gion: Financial Interests, Personal, Speaker’s Bureau: Roche, Genyca; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer. B. Bermejo: Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Pfizer, Lilly MSD, Palex, AstraZeneca; Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, MSD. M. Martinez- Garcia: Financial Interests, Personal, Speaker’s Bureau: Roche, Celgene, Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Roche; Financial Interests, Personal, Research Grant: Pfizer. C. Vieira: Financial Interests, Personal, Advisory Role: Grünenthal, Novartis, Lilly, Pfizer, MSD, Merck Serono, BMS, F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Grünenthal, Novartis, Lilly, Pfizer, MSD, Merck Serono, BMS, F. Hoffmann-La Roche Ltd. M. Sampayo: Financial Interests, Personal, Other, honoararia: MedSIR, Syntax for Science, Nestlé; Financial Interests, Personal, Advisory Role: MedSIR, Syntax for Science, Nestlé; Financial Interests, Personal, Speaker’s Bureau: MedSIR, Syntax for Science, Roche; Financial Interests, Personal, Research Grant: MedSIR, Syntax for Science, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MedSIR, Syntax for Science, Roche. A. Malfettone: Financial Interests, Personal, Full or part-time Employment: MedSIR. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Kyowa Kirin; Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F. Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Financial Interests, Personal, Stocks/Shares: MedSIR; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo. J.M. Pérez-Garcia: Financial Interests, Personal, Advisory Role: Roche, Lilly; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche. All other authors have declared no conflicts of interest.