Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase 
inhibitor. This phase Ia/Ib study investigated the safety, tolerability, 
pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in 
combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese 
patients with advanced solid tumors or non-squamous non-small cell lung cancer. 
A standard 3 + 3 dose escalation design was applied. In stage 1, 140, 260, or 
340 mg/day of pictilisib was administered once daily to 12 patients with 
advanced solid tumors. In stage 2, 260 or 340 mg/day of pictilisib was 
administered in combination with CP + BEV to 7 patients with advanced 
non-squamous non-small cell lung cancer. In stage 1, 1 of 6 patients in the 
340 mg/day cohort exhibited dose limiting toxicity (DLT) of grade 3 
maculopapular rash. The maximum plasma concentration and area under the curve of 
pictilisib were dose-dependent. A reduction in phosphorylated AKT in platelet 
rich plasma was observed. No patient had an objective anti-tumor response. In 
stage 2, DLT was observed in 1 of 3 patients in the 260 mg/day cohort (grade 3 
febrile neutropenia), and 2 of 4 patients in the 340 mg/day cohort (1 each of 
grade 3 febrile neutropenia and grade 3 febrile neutropenia/erythema 
multiforme). Partial responses were observed in 3 out of 7 patients. In 
conclusion, pictilisib was shown to have good safety and tolerability in 
Japanese patients with advanced solid tumors. A recommended dose of pictilisib 
in monotherapy was determined to be 340 mg once daily. For combination with 
CP + BEV, tolerability up to 260 mg/day was confirmed.