A Phase Ib/Ii Study Of Cancer Sternness Inhibitor Napabucasin (Bb608) Combined With Weekly Paclitaxel In Advanced Non-Small Cell Lung Cancer.

9093 Background: Napabucasin (BBI-608, BB608) is a first-in-class cancer stemness inhibitor that works through inhibiting the STAT3 pathway, and it has shown potent synergistic anti-tumor activity with paclitaxel in vivo. In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, BB608 plus weekly paclitaxel was well tolerated. Phase II accrual to disease-specific cohorts included patients with advanced, heavily pre-treated metastatic non-small cell lung cancer (NSCLC). Methods: Pts with metastatic squamous or non-squamous NSCLC who had progressed on prior systemic therapy were enrolled to assess safety, tolerability, and preliminary anti-cancer activity. BB608 was administered orally at a starting dose of 240 mg twice daily with paclitaxel 80 mg/m2 IV weekly 3 of every 4 weeks. A sample size of 40 set the bounds of the 90% CI at ±10% to 14%, assuming a disease control rate (DCR) of 60% to 80%. DCR is the proportion with stable disease (SD) of at least 8 weeks or objective partial (PR) or complete response (CR) per RECIST 1.1. Results: 27 pts were enrolled with a median number of 3 prior lines of systemic treatment; 26/27 pts (96%) had received prior taxane-based therapy. Treatment was well tolerated. Related grade 3 adverse events included diarrhea (n = 1) and hyponatremia (n = 1) and were rapidly reversible. For evaluable pts (n = 19), DCR was 79%, tumor regression occurred in 37%, and objective partial response (PR) in 16%. For evaluable non-squamous pts (n = 15), DCR was 87%, tumor regression occurred in 47%, and PR in 20%. Overall (ITT, n = 27), DCR was 56%, tumor regression occurred in 26%, and PR in 11%. Median progression free survival (mPFS) was 16 weeks and median overall survival (mOS) was 34 weeks. For non-squamous pts (ITT, n = 22), mPFS was 17 weeks and mOS was 37 weeks. Conclusions: Safety, tolerability, and encouraging signs of anti-cancer activity were observed in pts with heavily pretreated NSCLC who received BBI608 plus weekly paclitaxel. Objective response, tumor regression, durable disease control, and prolonged progression free survival and overall survival in this refractory population are notable, and further clinical evaluation is warranted. Clinical trial information: NCT01325441.