CHICAGO-The BRIGHTER trial, a phase III study, is underway to determine the effectiveness of the new drug, BBI-608, researchers reported during a poster session at the 2016 American Society of Clinical Oncology Annual Meeting in Chicago (Abstract TPS4144).
The primary objective of the trial is to assess the effect of BBI-608 plus weekly paclitaxel, versus a placebo and weekly paclitaxel on the overall survival of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
What is BBI-608?
An orally-administered first-in-class cancer stemness inhibitor, BBI-608 has a unique mechanism of action, according to Manish Shah, MD, study author and Medical Director of the Gastrointestinal Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian.
"BBI-608 blocks cancer stem cell self-renewal and survival by suppressing stemness pathways, including Stat3, a protein central to cancer progression," he explained. "This protein hasn't been targeted well in the past, making BBI-608 a distinctive treatment option."
Previous Research
Results from previous studies support the validity of a BBI-608 + paclitaxel combination for the treatment of gastric or GEJ adenocarcinoma.
A phase Ib study (J Clin Oncol 2014;32:5s) concluded that BBI-608 and weekly paclitaxel could be safely combined at a full dose. Encouraging anticancer activity in refractory gastric and GEJ adenocarcinoma was observed in this study as well as a subsequent phase II study (Journal of Clinical Oncology 2015;33:4069), according to researchers.
"There have been several preclinical trials that suggest that the unique properties of this compound leads to positive outcomes," Shah said. "Additionally, data from another early stage study showed anti-tumor and anti-metastatic activity in several different types of cancers, including stomach cancer."
Given these promising results, the BRIGHTER trial was initiated in North America, South America, Europe, Australia, and Asia.
Study Methodology
The BRIGHTER trial is a phase III, randomized double-blind study of BBI-608 and weekly paclitaxel versus placebo and weekly paclitaxel in patients with pretreated advanced gastric and GEJ adenocarcinoma.
Patients are randomized in a 1:1 ratio to receive BBI-608 480 mg or the placebo twice daily plus paclitaxel 80 mg/m2 IV, weekly, for 3 of every 4 weeks, according to researchers. Blood, plasma, and archival tissue will be assessed for biomarker analyses and quality of life will be measured.
"The study is in the second line setting," explained Shah. "Patients must have failed one prior line of therapy and cannot be refractory to taxanes."
"The phase III study is ongoing," he continued. "We are still recruiting patients and hope to finish recruitment in the next 6 to 12 months." As of February 2016, 364 patients were randomized (NCT02178956).
Impact on Practice
The results of this phase III trial have the potential to revolutionize treatment options for patients with advanced gastric and GEJ adenocarcinoma as well as a variety of other cancers.
"Unfortunately, the majority of patients with stomach cancer will still die of their disease, so it is our hope that this treatment plan could have a positive impact," Shah noted. "We hope to find that BBI-608 is a new option that will improve patient outcomes and if that is the case the next step is to get the drug approved.
"The practice implications are important anytime you bring a new drug with a new mechanism of action," he concluded. "There are many different types of cancers that could see positive outcomes through the utilization of this treatment strategy."
Catlin Nalley is an associate editor.