Reference Detail

Ref Type

Journal Article

PMID

(28331003)

Authors

Juric D, Krop I, Ramanathan RK, Wilson TR, Ware JA, Sanabria Bohorquez SM, Savage HM, Sampath D, Salphati L, Lin RS, Jin H, Parmar H, Hsu JY, Von Hoff DD, Baselga J

Title

Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer discovery	7	7	2017 Jul	704-715	Cancer Discov

URL

Abstract Text

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 at ≥3 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. Cancer Discov; 7(7); 704-15. ©2017 AACR.See related commentary by Rodon and Tabernero, p. 666This article is highlighted in the In This Issue feature, p. 653.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA H1047R	breast cancer	sensitive	Taselisib	Phase I	Actionable	In a Phase I trial, four patients with breast cancer harboring PIK3CA H1047R demonstrated a confirmed partial response when treated with Taselisib (GDC-0032) (PMID: 28331003).	28331003
PIK3CA H1047X	lung non-small cell carcinoma	sensitive	Taselisib	Phase I	Actionable	In a Phase I trial, a non-small cell lung carcinoma patient harboring a mutation at PIK3CA H1047 demonstrated a confirmed partial response when treated with Taselisib (GDC-0032) (PMID: 28331003).	28331003