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The CanStem111P trial, which was evaluating the combination of napabucasin, weekly nab-paclitaxel (Abraxane), and gemcitabine compared with nab-paclitaxel/gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma, will be discontinued due to futility.
Patricia S. Andrews
The CanStem111P trial, which was evaluating the combination of napabucasin, weekly nab-paclitaxel (Abraxane), and gemcitabine compared with nab-paclitaxel/gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma, will be discontinued due to futility, according to Boston Biomedical, the manufacturer of the investigational agent.1
The decision to stop the trial is based on a recommendation by the Independent Data and Safety Monitoring Board following a prespecified interim analysis of futility at 50% of total planned events. The committee did not raise any new safety concerns.
“Pancreatic cancer is an area of high unmet need and our hope was to develop a new therapeutic option for patients. We are disappointed with the results of this interim analysis and would like to express gratitude to the trial participants, their families, investigators and staff for their efforts and contributions to this study,” Patricia S. Andrews, chief executive officer of Boston Biomedical stated in a press release. “Boston Biomedical and our parent company, Sumitomo Dainippon Pharma Co., Ltd., remain committed to CanStem303C, a phase III trial of napabucasin in metastatic colorectal cancer, and to oncology as a key priority for the organizations.”
The company stated that it will work with CanStem111P (NCT02993731) investigators in order to complete the full findings. Moreover, full data will be published and presented at an upcoming medical meeting, and be provided to regulatory authorities.
The oral investigational agent napabucasin is bioactivated by NQO1, which generates reactive oxygen species (ROS) to affect multiple oncogenic cellular pathways, such as STAT3, which can lead to cell death.
Prior phase Ib/II napabucasin results, which were presented at the 2017 World Congress on Gastrointestinal Cancers, demonstrated early efficacy for the drug when used in combination with different standard chemotherapy backbones in patients with metastatic pancreatic adenocarcinoma.2
The multicenter trial comprised 66 patients with histologic or cytologic evidence of pancreatic adenocarcinoma in the intent-to-treat population, 49 (74%) of whom were treatment-naïve and 17 (26%) had received neoadjuvant treatment. All patients received oral napabucasin at 240 mg twice daily plus weekly nab-paclitaxel at 125 mg/m2 and gemcitabine at 1000 mg/m2 for 3 of 4 weeks until disease progression.
The median age was 64.5 years (range, 47-82), 53% were male, and the majority (59%) had an ECOG performance status of 1. The primary endpoint was safety and tolerability, as well as determining the recommended phase II dose.
Results showed that, of the 55 evaluable patients, 51 patients demonstrated a response, leading to a disease control rate of 93%, which comprised 1 complete response (CR), 26 partial responses (PRs), and 24 patients with stable disease. Moreover, the objective response rate (CR + PR) was 55%. Four patients in the evaluable group had progressive disease (PD); 3 progressed while on treatment and 1 patient experienced PD after discontinuing therapy due to toxicity.
Additional data demonstrated that the 1-year overall survival rate was 56% and the maturing progression-free survival was 7.1 months; all but 10 patients showed tumor reduction. Most patients showed decreased CA 19-9 levels from baseline; 73% of patients showed a ≥20% reduction, 73% showed ≥50%, and 37% of patients demonstrated ≥90% decrease in CA 19-9 levels.
Napabucasin is also being investigated in the ongoing phase III CanStem303C trial (NCT02753127) in patients with metastatic colorectal cancer, as well as in earlier-phase trials in multiple solid malignancies.