Abstract 349TiP
Background
TNBC has a high unmet need for novel therapies. Taxanes (T) are effective in advanced TNBC, but resistance often develops. PI3K pathway hyperactivation, driven by PIK3CA mutations and PTEN loss, can confer resistance to chemotherapy. ALP is an α-selective PI3K inhibitor (i). In SOLAR-1, ALP + fulvestrant prolonged progression-free survival (PFS) vs. PBO + fulvestrant in HR+, HER2–, PIK3CA-mutated advanced breast cancer (ABC). The combination of ALP + nab-PTX demonstrated promising activity in HER2– ABC in a phase I/II trial, which included TNBC patients.
Trial design
EPIK-B3 is a phase III trial in 3 parts evaluating ALP + nab-PTX as 1st or 2nd line of therapy (LoT) in advanced TNBC according to PIK3CA and PTEN status. Part A is a randomised, DB, PBO-controlled study in patients with PIK3CA mutation regardless of PTEN status. Part B1 is a single-arm, open-label study in patients with PTEN loss without PIK3CA mutation, and if preliminary efficacy is demonstrated, Part B2 will explore ALP + nab-PTX in the same patient population as Part B1 in a randomised, DB fashion. Key inclusion criteria are histologic diagnosis of advanced TNBC, ≤1 LoT for advanced disease, and measurable disease or either lytic/mixed lytic-blastic bone lesion with soft tissue component. Prior T therapy is allowed if treatment was completed ≥12 months to Day (D) 1 of Cycle 1, and best response was not progression. Key exclusion criteria are prior PI3Ki/mTORi/AKTi, clinically unstable CNS disease and/or type 1 or uncontrolled type 2 diabetes. In Parts A and B2, patients are randomised 1:1 to receive ALP or PBO + nab-PTX, stratified by metastatic LoT, HR status at initial breast cancer diagnosis, and prior immune checkpoint inhibitor therapy. ALP or PBO is given at 300 mg daily and nab-PTX at 100 mg/m2 IV on D1, 8, and 15 in 28-D cycles. For Parts A and B2, the primary endpoint is PFS with overall survival as a key secondary endpoint. For Part B1, best overall response after 6 months is the primary endpoint. Other endpoints include efficacy, safety, quality of life, and genomic biomarkers.
Clinical trial identification
NCT04251533.
Editorial acknowledgement
Medical editorial assistance was provided by Karlo Dumaup, from Healthcare Consultancy Group, LLC, funded by Novartis Pharmaceuticals.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
P. Sharma: Honoraria (self), Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Puma Biotechnology; Honoraria (self): Myriad Genetic Laboratories; Honoraria (self): Seattle Genetics. A. Farooki: Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genentech; Advisory/Consultancy: Novo Nordisk. P.A. Fasching: Honoraria (self), Research grant/Funding (self): Novartis; Research grant/Funding (self): Biontech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene ; Honoraria (self): Daiichi-Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Eisai; Honoraria (self): Puma; Research grant/Funding (self): Cepheid; Honoraria (self): Lilly. S. Loi: Research grant/Funding (institution): Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Novartis; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Merck; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Roche-Genentech; Research grant/Funding (institution): Puma Biotechnology; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Acted as consultant (not compensated) : Seattle Genetics; Advisory/Consultancy, Acted as consultant (not compensated) : AstraZeneca; Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Acted as consultant (not compensated): BMS. K. Peterson: Honoraria (self): Eli Lilly ; Honoraria (self), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Travel/Accommodation/Expenses: Nektar. A. Prat: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, family member is an employee : Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Boehringer; Advisory/Consultancy, Research grant/Funding (institution): Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Nanostring Technologies; Research grant/Funding (institution): Incyte. D. Tripathy: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Nektar; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sellas Life Sciences; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Genomic Health; Advisory/Consultancy, Research grant/Funding (institution): Polyphor. B. Xu: Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: Eisai. D.A. Yardley: Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Research grant/Funding (institution): Genentech; Advisory/Consultancy: Immunomedics, Inc.; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Odonate Therapeutics; Honoraria (institution): R-Pharm US; Honoraria (institution): Seattle Genetics; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Dana-Farber Cancer Institute; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): MacroGenics; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): NSABP; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): US Oncology. D. Mills: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. G. Klauss: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. C. Wong: Shareholder/Stockholder/Stock options, Full/Part-time employment, Patents, royalties, other intellectual property: Novartis. F. André: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Roche.