Sumitomo Dainippon Pharma is unblinding the global Phase III BRIGHTER study evaluating its cancer stemness inhibitor napabucasin (BBI-608) in patients with gastric and gastroesophageal junction (GEJ) cancer on the recommendation of the study’s independent data and safety monitoring board (DSMB). A planned interim analysis by the DSMB indicated that the study was unlikely to meet its primary overall survival (OS) endpoint.
Napabucasin is a first-in-class, orally administered, STAT3-targeting small-molecule anticancer drug discovered by Cambridge, MA-based Boston Biomedical, which Sumitomo Dainippon Pharma acquired in 2012. Boston Biomedical CEO Patricia S. Andrews admitted the firm was “disappointed” with the interim BRIGHTER study data. “Advanced gastric/GEJ cancer is a tumor type with high unmet need, and our hope was to develop a new therapeutic option for these patients,” she said. “We remain committed to our ongoing studies with napabucasin as well as our other first-in-class investigational compounds.”
The BRIGHTER study was designed to evaluate the efficacy and safety of napabucsin plus weekly paclitaxel, compared with paclitaxel alone, in 714 patients with advanced gastric and GEJ cancer who have previously received one prior platinum/fluoropyrimidine-containing treatment regimen. As well as the primary OS endpoint, the BRIGHTER study is designed to assess secondary endpoints, including progression-free survival (PFS) and OS and PFS in a biomarker-defined subpopulation, objective response rate, disease control rate, and safety.
Napabucasin is separately being evaluated in the Phase III CanStem303C trial in colorectal cancer and CanStem111P in pancreatic cancer. The CanStem111P study was initiated in February and is evaluating napabucasin in combination with standard-of-care nab-paclitaxel plus gemcitabine therapy in patients with metastatic pancreatic cancer. The CanStem303C study, initiated in October 2016, is evaluating napabucasin in combination with standard-of-care FOLFIRI (folinic acid, fluorouracil, and irinotecan) therapy in patients with previously treated metastatic colorectal cancer.
Boston Biomedical is exploiting a suite of proprietary platform technologies to discover and develop anticancer therapies that target cancer stem cell (CSC) pathways. The firm’s clinical pipeline is headed by napabucasin and a second stemness inhibitor, amcasertib (BBI-503), which is designed to inhibit cancer stemness pathways, including Nanog, by targeting stemness kinases. Amcasertib is undergoing multiple Phase I and Phase II studies as monotherapy and combination therapy for treating a range of tumor types.
Positive data from a Phase Ib/II study evaluating amcasertib monotherapy in patients with advanced adenoid cystic carcinoma (ACC) and advanced head and neck cancers was presented at the 2017 American Society of Clinical Oncology (ASCO) meeting in Chicago. Also at ASCO, Boston Biomedical presented positive data from Phase I/II studies with napabucasin across seven tumor types.