Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center

SIMPLE SUMMARY: BBI608 is an investigational reactive oxygen species generator that affects several molecular and oncogenic pathways, including the STAT3 pathway, and may overcome resistance to immune checkpoint inhibitors. We investigated BBI608 combined with immunotherapy (ipilimumab, pembrolizumab, or nivolumab) in patients with advanced cancer. Treatment was well tolerated overall. Only 2 of 12 patients had Grade 3 diarrhea. Five patients treated with BBI608/nivolumab had prolonged disease stabilization lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Prospective studies of BBI608 are warranted. ABSTRACT: Background: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. Methods: BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. Results: From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31–78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1–2, n = 3; G3, n = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Conclusions: Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted.