Phase Ib/II study of cancer stem cell (CSC) inhibitor BBI608 combined with paclitaxel in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma.

Identifying and targeting cancer stem cells in the treatment of gastric cancer

“…56 A phase 1b/2 extension study (National Clinical Trials identifier NCT01325441; www.clinicaltrials.gov) of napabucasin combined with paclitaxel was conducted in patients with advanced gastric and GEJ adenocarcinoma. 57 All patients received daily, continuous napabucasin 480 mg twice daily or 500 mg twice daily plus weekly paclitaxel 80 mg/m 2 for 3 of every 4 weeks in a 28-day cycle. Objective tumor response assessments occurred every 8 weeks.…”

“…Results from the study indicate that napabucasin plus weekly paclitaxel is well tolerated in patients with advanced gastric/GEJ cancer, and activity was observed even in heavily pretreated patients. 57 Continued evaluation of the combination of napabucasin and paclitaxel in patients with gastric/GEJ cancer who received Cancer Stems Cells in Gastric Cancer/Bekaii-Sabb and El-Rayes Cancer April 15, 2017 only 1 prior line of therapy is currently underway in the phase 3 BBI608 Plus Weekly Paclitaxel to Treat Gastric and Gastroesophageal Junction Cancer (BRIGHTER) study, as described below.…”

Novel STAT 3 inhibitors for treating gastric cancer

“…This review has highlighted some of the new STAT3 inhibitors coming through in early phase clinical trials. Of those discussed, napabucasin appears to be the most developed and has shown promise when partnered with paclitaxel [38][39][40], an accepted second-line drug with demonstrable efficacy in gastric cancer [45], and certainly the results of the BRIGHTER study will be eagerly awaited. Of note, given the toxicities noted to date with the STAT3 inhibitors, careful attention should be paid to the propensity for gastrointestinal upset, namely nausea, vomiting, and diarrhea, and active management of these toxicities will need to be addressed as these symptoms may be prominent in this patient group.…”

“…In 26 patients who had failed prior taxane (median three prior lines of treatment), ORR and disease control rate were 11% (2/19) and 68% (13/19), respectively, with median OS of 33 weeks. In a subset of patients who received only one prior line of therapy without a taxane, the ORR was 50% (3/6) with a disease control rate of 83% (4/6) [39].…”

Advances in Systemic Therapy for Metastatic or Advanced Gastric Cancer

“…42 Encouraging anticancer activity of BBI608 and paclitaxel in refractory AGC was observed in a phase Ib and subsequent phase II study including 46 patients with AGC with an overall response rate (ORR) of 31% and disease control rate of 75%. 43 Currently, the phase III BRIGHTER trial (ClinicalTrials.gov identifier: NCT02178956) is ongoing to compare BBI608 plus paclitaxel and placebo plus paclitaxel after first-line chemotherapy for patients with AGC.…”