Phosphatidylinositol 3-kinase (PI3K) pathway activation is associated with 
resistance to paclitaxel in solid tumors. We assessed the safety and activity of 
alpelisib, an oral, selective PI3K p110α inhibitor, plus paclitaxel in patients 
with advanced solid tumors. This Phase Ib, multicenter, open-label, dose-finding 
study, with a planned dose-expansion phase of alpelisib once daily (QD) plus 
fixed-dose paclitaxel, recruited patients with advanced solid tumors. For the 
dose-finding phase, the primary objective was determination of maximum tolerated 
and/or recommended Phase II dose of alpelisib plus paclitaxel, and the secondary 
objectives included the assessment of safety for this combination. From March 
2014 to August 2016, 19 patients with advanced solid tumors were treated with 
alpelisib QD (300 mg, n=6; 250 mg, n=4; 150 mg, n=9) plus paclitaxel (80 mg/m2, 
per standard of care). During dose finding, five of 12 (41.7%) evaluable 
patients for MTD determination experienced dose-limiting toxicities: alpelisib 
300 mg, Grade 2 hyperglycemia (n=1); alpelisib 250 mg, Grade 2 hyperglycemia 
(n=1), Grade 4 hyperglycemia and Grade 3 acute kidney injury (n=1); and 
alpelisib 150 mg, Grade 2 hyperglycemia (n=1) and Grade 4 leukopenia (n=1). The 
MTD of alpelisib when administered with paclitaxel was 150 mg QD. Most frequent 
all-grade AEs were diarrhea (73.7%; Grade 3/4 10.5%) and hyperglycemia (57.9%; 
Grade 3/4 31.6%). The planned dose-expansion phase was not initiated. Alpelisib 
plus paclitaxel has a challenging safety profile in patients with advanced solid 
tumors. This study was closed following the completion of the dose-finding 
phase.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02051751.