A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated non-squamous non-small cell lung cancer.

• DOI: 10.1200/jco.2017.35.15_suppl.9052
• Publication Date: 2018-09-06T15:51:19Z
• Authors: Carlos Becerra; Wahid Tewfik Hanna; Stephen Lane Richey; Gregory Michael Cote; Scott Andrew Laurie; Adrian Langleben; Yuan Gao; Wei Li; Youzhi Li; Matthew Hitron; Chiang Li
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

9052 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A phase II expansion cohort was opened for pts with advanced non-small cell lung cancer (NSCLC). Methods: Pts with metastatic non-squamous NSCLC were enrolled to confirm safety and preliminary anti-cancer activity. Prior platinum-based systemic therapy was required, and patients with an EGFR or ALK mutation required appropriately targeted therapy. Napabucasin was administered orally at a starting dose of 240 or 480 mg BID with PTX 80 mg/m2 IV weekly 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed every 8 weeks per RECIST 1.1. Results: A cohort of 23 pts with advanced non-squamous NSCLC was evaluated. The median number of prior systemic treatment lines was 3, including taxane-based therapy in 100% and immune checkpoint inhibitor in 48% (n = 11). Treatment was well tolerated; related grade 3 AE included diarrhea (n = 4) and fatigue (n = 1). The objective response rate was 26% (6 partial responses [PR]) and the disease control rate (DCR; proportion with SD at 8 weeks plus PR per RECIST) was 70% (n = 16). Tumor regression, including PR, occurred in 35% (n = 8). The median progression-free survival (mPFS) was 5.4 months, and 43% (n = 10) of pts were alive and free of progression at the 24 week time-point or longer. The median overall survival (mOS) was 11.0 months, and 30% (n = 7) of pts were alive for 52 weeks or longer. Conclusions: Clinical safety and encouraging signs of anti-cancer activity were observed in pts with heavily pretreated non-squamous NSCLC who received napabucasin plus weekly paclitaxel. The objective response rate, progression free survival, and overall survival in this population warrant further clinical evaluation and a controlled phase 2/3 trial (CanStem43L) has been initiated. Clinical trial information: NCT01325441.