Abstract P3-14-10: Phase Ia/Ib study of taselisib (GDC-0032), a potent and selective phosphoinositide 3-kinase inhibitor, in Japanese patients with advanced solid tumors or hormone receptor-positive locally advanced or metastatic breast cancer (JO29196 study)
Authors: T Kobayashi, K Nakano, J Tomomatsu, E Nara, Y Ito, K Kobayashi, I Fukada, K Araki, A Shimomura, T Shimoi, M Kodaira, M Yunokawa, K Yonemori, C Shimizu, K Nakamura, N Kotani, M Inatani, K Tamura, S Takahashi
Journal: Cancer Research (2016)

Abstract Background: Taselisib (GDC-0032) is an orally bioavailable, potent and selective phosphoinositide 3-kinase (PI3K) inhibitor. Preclinical data showed that taselisib had increased antitumor activity against PIK3CA (gene encoding the PI3Kα isoform) mutant tumors. This study aimed to investigate the safety, tolerability and pharmacokinetics (PK) of taselisib as monotherapy and in combination with fulvestrant in Japanese patients (pts). Materials and methods: A 3+3 design was used. In Phase Ia, pts with advanced solid tumors received taselisib tablet monotherapy (2, 4 or 6 mg once daily [QD]), and safety and PK were evaluated. In Phase Ib, pts with hormone receptor-positive locally advanced or metastatic breast cancer received taselisib (2 or 4 mg QD) in combination with fulvestrant (500 mg at a time), and safety and PK were evaluated. Maximal administered doses of 6 mg QD as a single agent and 4 mg QD in combination with fulvestrant were based upon prior clinical trial experience with taselisib (Juric D. et al. AACR 2013, Abstract LB-64; Juric D. et al. SABCS 2013, Abstract PD1-3). Results: As of 15 Mar 2015, 9 pts (PIK3CA mutant: 2 pts) were enrolled in Phase Ia and 3 pts in Phase Ib. Phase Ia dose-escalation study has been completed and Phase Ib is ongoing. In Phase Ia, no dose-limiting toxicity (DLT) was observed at any dose level tested (maximum administered dose of 6 mg QD). Common (≥3 pts) adverse reactions (ARs) were stomatitis (4 pts), rash (3 pts) and diarrhea (3 pts); the only Grade ≥3 AR was neutropenia (1 pt). Partial response was observed in 1 pt who received taselisib 4 mg and had a PIK3CA mutant breast tumor. Stable disease was observed in 4 pts. Cmax and AUC indicated a dose-proportional PK profile of taselisib within the dose range tested. Moreover, taselisib PK in Japanese pts was consistent with the PK reported from North American and European pts (Juric D. et al. AACR 2013, Abstract LB-64). In Phase Ib, 3 pts received taselisib 2 mg in combination with fulvestrant and no DLT was observed. Preliminary ARs were similar to those with monotherapy and no Grade ≥3 AR was reported. Confirmation of tolerability of taselisib 4 mg in combination with fulvestrant is under evaluation. Conclusion: Taselisib monotherapy was well tolerated in Japanese pts up to a dose of 6 mg, which is the recommended dose in non-Japanese pts. Promising preliminary activity of monotherapy was observed in advanced solid tumors, especially in a pt with PIK3CA mutant tumor. The combination of taselisib 2 mg with fulvestrant is well tolerated. Investigation of tolerability of taselisib 4 mg in combination with fulvestrant is ongoing. Final results of this study will be presented here at the Symposium this year. Citation Format: Kobayashi T, Nakano K, Tomomatsu J, Nara E, Ito Y, Kobayashi K, Fukada I, Araki K, Shimomura A, Shimoi T, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Nakamura K, Kotani N, Inatani M, Tamura K, Takahashi S. Phase Ia/Ib study of taselisib (GDC-0032), a potent and selective phosphoinositide 3-kinase inhibitor, in Japanese patients with advanced solid tumors or hormone receptor-positive locally advanced or metastatic breast cancer (JO29196 study). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-14-10.