Phase II Study of Taselisib in PIK3CA -Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I.

Purpose: PIK3CA mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in PIK3CA -mutant breast cancer. Whether PIK3CA mutations predict sensitivity to taselisib in other cancer types is unknown. National Cancer Institute-Molecular Analysis for Therapy Choice Arm EAY131-I is a single-arm, phase II study of the safety and efficacy of taselisib in patients with advanced cancers.
Methods: Eligible patients had tumors with an activating PIK3CA mutation. Patients with breast or squamous cell lung carcinoma, or whose cancer had KRAS or PTEN mutations, were excluded. Patients received taselisib 4 mg, orally once daily continuously, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included progression-free survival (PFS), 6-month PFS, overall survival (OS), and identification of predictive biomarkers.
Results: Seventy patients were enrolled, and 61 were eligible and initiated protocol therapy. Types of PIK3CA mutations included helical 41 of 61 (67%), kinase 11 of 61 (18%), and other 9 of 61 (15%). With a median follow-up of 35.7 months, there were no complete or partial responses. Six-month PFS was 19.9% (90% CI, 12.0 to 29.3) and median PFS was 3.1 months (90% CI, 1.8 to 3.7). Six-month OS was 60.7% (90% CI, 49.6 to 70.0) and median OS was 7.2 months (90% CI, 5.9 to 10.0). Individual comutations were too heterogeneous to correlate with clinical outcome. Fatigue, diarrhea, nausea, and hyperglycemia were the most common toxicities, and most were grade 1 and 2.
Conclusion: In this study, taselisib monotherapy had very limited activity in a heterogeneous cohort of heavily pretreated cancer patients with PIK3CA -mutated tumors; the presence of a PIK3CA mutation alone does not appear to be a sufficient predictor of taselisib activity.
Competing Interests: Ian E. KropEmployment: Freeline Therapeutics (I), PureTech (I), AMAG Pharmaceuticals (I)Leadership: AMAG Pharmaceuticals (I), Freeline Therapeutics (I), PureTech (I)Stock and Other Ownership Interests: AMAG Pharmaceuticals (I), Freeline Therapeutics (I), PureTech (I)Honoraria: Genentech/Roche, AstraZeneca, CelltrionConsulting or Advisory Role: Genentech/Roche, Seattle Genetics, Daiichi Sankyo, Macrogenics, Novartis, Merck, Bristol Myers Squibb, AstraZenecaResearch Funding: Genentech (Inst), Pfizer (Inst) Juneko E. Grilley-OlsonConsulting or Advisory Role: Bayer, Chimerix, Kura Oncology, SpringWorks TherapeuticsResearch Funding: NanoCarrier (Inst), Genentech (Inst), Seattle Genetics (Inst), Pfizer (Inst), Loxo (Inst), Astellas Pharma (Inst), Iovance Biotherapeutics (Inst) Josh D. LauringEmployment: Janssen Research & DevelopmentStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Galderma (I), Regeneron (I), Novartis (I)Speakers' Bureau: Galderma (I), AbbVie (I), Pfizer (I)Patents, Royalties, Other Intellectual Property: I intermittently receive royalty payments for cell lines created in my laboratory, which are licensed for commercial sale to Horizon Discovery, Ltd by Johns Hopkins UniversityTravel, Accommodations, Expenses: Galderma (I), AbbVie (I) Edith P. MitchellLeadership: Corvus PharmaceuticalsHonoraria: Sanofi, ExelixisConsulting or Advisory Role: Genentech, Novartis, Merck, Bristol Myers SquibSpeakers' Bureau: IpsenResearch Funding: Genentech (Inst), sanofi (Inst) Robert J. GrayResearch Funding: Agios, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Genentech/Roche, Genomic Health, Genzyme, GlaxoSmithKline, Janssen-Ortho, Onyx, Pfizer, Sequenta, Syndax, Novartis, Takeda, AbbVie, Sanofi, Merck Sharp & Dohme P. Mickey WilliamsResearch Funding: Illumina (Inst)Patents, Royalties, Other Intellectual Property: I was a coinventor of the DLBCL cell of origin patent recently filed by the NIH Stanley R. HamiltonResearch Funding: Minerva Biotechnologies, Intima James M. FordThis author is the Editor-in-Chief for JCO Precision Oncology. Journal policy recused the author from having any role in the peer review of this manuscript.Research Funding: Genentech (Inst), AstraZeneca (Inst), Puma Biotechnology (Inst), Pfizer (Inst), Merus (Inst), Bayer (Inst), Incyte (Inst) Agustin A. GarciaConsulting or Advisory Role: Biotheranostics, GlaxoSmithKlineResearch Funding: Advenchen Laboratories (Inst), Seattle Genetics (Inst), Merck (Inst), Iovance Pharm (Inst) Xingwei D. SuiConsulting or Advisory Role: Novartis Robert D. SiegelResearch Funding: Merck (Inst), Mirati Therapeutics (Inst), GRAIL (Inst), Altor BioScience (Inst), Galera Therapeutics (Inst), Apollomics (Inst), Strata Oncology (Inst), Arcus Biosciences (Inst), Bristol Myers Squibb (Inst), Cancer Insight (Inst), Puma Biotechnology (Inst), Conjupro Biotherapeutics (Inst), Razor Genomics (Inst), Sanofi (Inst), Seattle Genetics (Inst)Other Relationship: American Board of Internal Medicine (ABIM) Brian M. SlomovitzConsulting or Advisory Role: Clovis Oncology, AstraZeneca, Genentech, Incyte, Agenus, GlaxoSmithKline, GOG Foundation, Myriad Genetics, Merck, Eisai Carlos L. ArteagaStock and Other Ownership Interests: Provista DiagnosticsConsulting or Advisory Role: Novartis, Lilly, Sanofi, Radius Health, Taiho Pharmaceutical, Puma Biotechnology, Merck, Origimed, Immunomedics, Daiichi Sankyo, Athenex, Astrazeneca, ArvinasResearch Funding: Pfizer, Lilly, TakedaOther Relationship: Susan G. Komen for the Cure Lyndsay N. HarrisPatents, Royalties, Other Intellectual Property: Philips Healthcare Peter J. O'DwyerConsulting or Advisory Role: GenentechResearch Funding: Bristol Myers Squibb (Inst), Pfizer (Inst), Novartis (Inst), Genentech (Inst), Mirati Therapeutics (Inst), Celgene (Inst), GlaxoSmithKline (Inst), BBI Healthcare (Inst), Pharmacyclics (Inst), Five Prime Therapeutics (Inst), Forty Seven (Inst), Amgen (Inst), H3 Biomedicine (Inst), Taiho Pharmaceutical (Inst), Array BioPharma (Inst), Lilly/ImClone (Inst), Syndax (Inst), Syndax (Inst), Syndax (Inst), Syndax (Inst), syndax (Inst), Minneamrita Therapeutics (Inst)Expert Testimony: Lilly, Dai-ichi Sankyo Alice P. Chen(OPTIONAL) Uncompensated Relationships: Frontiers in Medicine Keith T. FlahertyStock and Other Ownership Interests: Clovis Oncology, Loxo, X4 Pharma, Strata Oncology, PIC Therapeutics, Shattuck Labs, Apricity Health, Oncoceutics, FOGPharma, Tvardi Therapeutics, Checkmate Pharmaceuticals, Kinnate Biopharma, Scorpion Therapeutics, ALX Oncology, xCures, Monopteros Therapeutics, Vibliome Therapeutics, Transcode Therapeutics, Soley TherapeuticsConsulting or Advisory Role: Novartis, Lilly, Oncoceutics, Tvardi Therapeutics, Takeda, Boston Biomedical, Debiopharm Group, FOGPharmaNo other potential conflicts of interest were reported.