The makers of rilotumumab (Amgen) have halted all clinical trials of the drug in advanced gastric cancer, following a planned safety review of a phase III study that showed an increase in the risk of death with the study drug.
Rilotumumab is a fully-human monoclonal antibody, designed to inhibit the hepatocyte growth factor/scatter factor:MET pathway. Inhibiting this pathway has the potential to reduce cell proliferation and prevent the migration of tumor cells, according to Amgen. The drug was under investigation in two phase III clinical trials, RILOMET-1 and 2, both of which will now be stopped. The interim safety review found an increase number of deaths vs chemotherapy alone, and the company says the protocol-defined futility criteria likely would have been met at a March 2015 analysis.
In a phase II trial of rilotumumab in locally advanced or metastatic gastric or gastroesophageal cancer, the drug did improve median overall survival specifically in patients with high MET expression, from 5.7 months to 11.1 months, yielding a hazard ratio of 0.29 (95% CI, 0.11-0.76). However, in those with low MET expression, there was a non-significant trend toward reduced survival, with an HR of 1.84 (95% CI, 0.78-4.34).
Both of the phase III studies included patients with MET-positive tumors, though MET expression levels were not specified, according to ClinicalTrials.gov. The RILOMET-1 study randomized patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to epirubicin, cisplatin, and capecitabine with either rilotumumab or placebo. RILOMET-2 treated patients with the same characteristics with either cisplatin and capecitabine along with placebo or cisplatin and capecitabine with rilotumumab.
The first of the two trials began in October 2012 and was planned to enroll 600 patients. RILOMET-2 began only this past July, with a planned enrollment of 450 patients.
“While we are disappointed with these results, we will work with lead investigators to further analyze the data in order to help inform future research and therapies in this area,” said Amgen’s executive vice president of research and development Sean E. Harper, MD, in a press release. “There is a high unmet need for new treatments to address advanced gastric cancer, one of the leading causes of cancer death worldwide.”
Gastric cancer caused 723,000 deaths around in the world in 2012, according to the World Health Organization, making it the third most common cause of cancer death after lung and liver cancer. Therapy options are limited for advanced gastric cancer, though the US Food and Drug Administration did recently approve ramucirumab for this indication after a positive phase III trial.