A phase 1b study of the cancer stem cell inhibitor BBI608 administered with paclitaxel in patients with advanced malignancies.

Second-line chemotherapy for patients with advanced gastric cancer

“…In a phase I trial of a combination of weekly paclitaxcel and BBI-608 in patients with solid cancer, five patients with gastric or EGJ cancer were enrolled. Tumor reduction was observed in three of the five patients (45%, 48%, and 24% respectively), and stable disease was maintained in two patients for 5 months or more [57]. In a phase I trial in six Japanese patients with gastric or EGJ cancer, the response rate was 33.3%, and one of the six patients was reported to maintain the response for 7.5 months or more [58].…”

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

“…gov), patients with advanced solid tumors received napabucasin plus weekly paclitaxel. 56 In total, 24 patients received continuous oral administration of escalating doses of napabucasin in combination with paclitaxel 80 mg/m 2 weekly for 3 of every 4 weeks of a 28-day cycle. Napabucasin was received by 3 patient dose cohorts of 200 mg twice daily, 400 mg twice daily, and 500 mg twice daily.…”

“…In this study, napabucasin plus weekly paclitaxel was safely combined and produced antitumor activity across several tumor types, particularly in patients who had gastric and GEJ adenocarcinoma. 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.…”

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.…”

“…Of five patients with refractory gastric/gastro oesophageal junction (GEJ), two had partial responses with 48% and 45% regression, one had stable disease with 25% regression, and two (who had failed prior taxane) had prolonged stable disease of >24 weeks. Tumor regression or stable disease of >16 weeks was also seen in patients with platinum-resistant ovarian cancer (one of two), melanoma (two of three), bladder (one of three), and NSCLC (one of one) [38].…”