Brief Report: SWOG S1400B (), A Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study)

Background: S1400B is a biomarker-driven Lung-MAP sub-study evaluating the phosphatidylinositide 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (SqNSCLC). Methods: Eligible patients had tumoral PIK3CA alterations by next generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4 mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by RECIST 1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS) and duration of response (DoR). Results: Twenty-six patients treated with taselisib comprised the full eligible population (FEP); 21 patients comprised the PAP. Median age in FEP was 68 y (53–83), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% RR, 95% CI 0%−24%). Two possibly treatment-related deaths (1 respiratory failure, 1 cardiac arrest) were observed; 1 patient had Grade 4 and 11 had Grade 3 adverse events. Median PFS and OS in the PAP were 2.9 months (95% CI, 1.8–4.0 mos) and 5.9 months (95% CI, 4.2–7.8 mos), respectively. These numbers were nearly the same in the FEP. Conclusions: Study S1400B evaluating taselisib in PIK3CA altered SqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in SqNSCLC.