A phase 1b/2 study of napabucasin with weekly paclitaxel in advanced, previously treated platinum resistant ovarian cancer.

Abstract

5548 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 patients with platinum resistant ovarian cancer. Methods: Pts with advanced ovarian cancer who had disease progression either during or in the 6 months following platinum-based systemic therapy were enrolled. napabucasin was administered orally at a starting dose of 240, 480, or 500 mg twice daily with PTX 80 mg/m2 IV weekly on 3 of every 4 weeks. AEs were evaluated using CTCAE v4.03 and objective assessments were performed per RECIST 1.1 every 8 weeks. Results: A total of 98 pts were enrolled. The average number of prior lines of systemic treatment was 3.5, including prior taxane-based therapy in 100% of patients. Treatment was well tolerated. Related grade 3 adverse events occurring ≥ 5% of pts included diarrhea (12.2%) and vomiting (5.1%). Among pts who received RECIST evaluation (n = 76), the disease control rate (DCR, proportion with SD at 8 weeks + PR + CR) was 65%, and the objective response rate (ORR, PR+CR) was 20%, with complete response in 3 pts (4%). In all patients (ITT, n = 98), the median progression-free survival (mPFS) was 3.0 months and median overall survival (mOS) was 9.3 months. Conclusions: Clinical safety and encouraging signs of anti-cancer activity, including three complete responses, were observed in pts with pre-treated platinum resistant ovarian cancer who received treatment with napabucasin plus weekly PTX. Further clinical evaluation in controlled trials is warranted. Clinical trial information: NCT01325441.