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

• DOI: 10.1200/jco.2017.35.15_suppl.5548
• Publication Date: 2018-09-06T15:46:45Z
• Authors: Carlos Becerra; Agustin A. Garcia; John L. Hays; Michael W. Method; Stephen Lane Richey; Adrian Langleben; Donald A. Richards; Gregory Michael Cote; Kimiko Kossler; Wei Li; Youzhi Li; Matthew Hitron; Chiang Li
• Keywords: Taxane; Tolerability

5548 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of stem cells (Li et al PNAS 112 (6):1839, 2015). has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In phase Ib dose escalation study in patients (pts) advanced solid tumors, napabucasin plus weekly PTX was well tolerated. A II expansion cohort opened for platinum resistant ovarian cancer. Methods: Pts who had disease progression either during or the 6 months following platinum-based systemic therapy were enrolled. administered orally at starting 240, 480, 500 mg twice daily 80 mg/m2 IV on 3 every 4 weeks. AEs evaluated using CTCAE v4.03 objective assessments performed per RECIST 1.1 8 Results: total 98 pts The average number prior lines treatment 3.5, including taxane-based 100% patients. Treatment Related grade adverse events occurring ≥ 5% included diarrhea (12.2%) vomiting (5.1%). Among received evaluation (n = 76), control rate (DCR, proportion SD weeks + PR CR) 65%, response (ORR, PR+CR) 20%, complete (4%). all (ITT, n 98), median progression-free survival (mPFS) 3.0 overall (mOS) 9.3 months. Conclusions: Clinical safety encouraging signs anti-cancer activity, three responses, observed pre-treated PTX. Further clinical controlled trials warranted. trial information: NCT01325441.