Phase I dose-escalation study of taselisib, an oral PI3K inhibitor, in patients with advanced solid tumors

Dejan Juric, Ian Krop, Ramesh K. Ramanathan, Timothy R. Wilson, Joseph A. Ware, Sandra M. Sanabria Bohorquez, Heidi M. Savage, Deepak Sampath, Laurent Salphati, Ray S. Lin, Huan Jin, Hema Parmar, Jerry Y. Hsu, Daniel D. Von Hoff, José Baselga

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


Taselisib is a potent and selective tumor growth inhibitor through PI3K pathway suppression. Thirty-four patients with locally advanced or metastatic solid tumors were treated (phase I study, modified 3+3 dose escalation; 5 cohorts; 3–16 mg taselisib once-daily capsule). Taselisib pharmacokinetics were dose-proportional; mean half-life was 40 hours. Frequent dose-dependent, treatment-related adverse events included diarrhea, hyperglycemia, decreased appetite, nausea, rash, stomatitis, and vomiting. At 12 and 16 mg dose levels, dose-limiting toxicities (DLT) were observed, with an accumulation of higher-grade adverse events after the cycle 1 DLT assessment window. Pharmacodynamic findings showed pathway inhibition at3 mg in patient tumor samples, consistent with preclinical PIK3CA-mutant tumor xenograft models. Confirmed response rate was 36% for PIK3CA-mutant tumor patients with measurable disease [5/14: 4 breast cancer (3 patients at 12 mg); 1 non–small cell lung cancer], where responses started at 3 mg, and 0% in patients with tumors without known PIK3CA hotspot mutations (0/15). Significance: Preliminary data consistent with preclinical data indicate increased antitumor activity of taselisib in patients with PIK3CA -mutant tumors (in comparison with patients with tumors without known activating PIK3CA hotspot mutations) starting at the lowest dose tested of 3 mg, thereby supporting higher potency for taselisib against PIK3CA -mutant tumors.

Original languageEnglish (US)
Pages (from-to)704-715
Number of pages12
JournalCancer discovery
Issue number7
StatePublished - Jul 2017

ASJC Scopus subject areas

  • Oncology


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