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

Cancers

David Vining¹  Graciela M. Nogueras Gonzalez²  Henry Hiep Vo³  Daniel D. Karp³  Apostolia-Maria Tsimberidou³  I-Wen Song³  Carrie Cartwright³  Michael Karol⁴  Yuran Xie⁴  Matthew Hitron⁴ 

[1] Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA;Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA;Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA;Sumitomo Dainippon Pharma Oncology, 640 Memorial Drive, Cambridge, MA 02139, USA;

关键词: advanced cancer;    clinical trial;    BBI608;    targeted therapy;    immunotherapy;    checkpoint inhibitor;   

DOI  :  10.3390/cancers14051330

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown