This article is more than 5 years old. Information may no longer be current.
Enrollment of demcizumab trials halted after pancreatic cancer study misses primary endpoint
Click Here to Manage Email Alerts
A phase 2 trial designed to evaluate demcizumab in combination with paclitaxel plus gemcitabine in treatment-naive patients with metastatic pancreatic cancer failed to meet its primary endpoint of PFS, according to the drug’s manufacturer.
As a result, OncoMed Pharmaceuticals intends to halt the trial, as well as discontinue enrollment in its other trials that involve demcizumab (OMP-21M18).
The randomized phase 2 YOSEMITE trial evaluated the safety and efficacy of demcizumab — a humanized monoclonal antibody that targets Delta-like Ligand 4 — plus standard chemotherapy as first-line treatment for patients with metastatic pancreatic cancer.
Researchers randomly assigned 204 patients to one of the following:
- Paclitaxel, gemcitabine and placebo (n = 68);
- Paclitaxel, gemcitabine and one 70-day truncated course of demcizumab, given once every 2 weeks (n = 71); or
- Paclitaxel, gemcitabine and two 70-day truncated courses of demcizumab, separated by a 98-day period without demcizumab (n = 65).
PFS served as the primary endpoint. Secondary endpoints included OS, overall response rate, pharmacokinetics, immunogenicity, safety and biomarker analyses.
Results showed no significant difference in PFS among treatment groups. Researchers reported median PFS of 5.4 months (HR = 1.03) among patients who received the single course of demcizumab and 5.5 months (HR = 0.83) among those who received two courses.
Researchers reported median OS of 13.2 months among all demcizumab-treated patients, whereas median OS had not been reached in the placebo group (HR = 1.02). Median OS was 10.6 months (HR = 1.2) among those who received one course of demcizumab and 13.3 months (HR = 0.87) among those who received two courses.
Investigators reported a higher ORR among patients assigned placebo (41.2% vs. 33.1%), but a higher clinical benefit rate among demcizumab-treated patients (74.3% vs. 70.6%).
“Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial,” Paul J. Hastings, chairman and CEO of OncoMed Pharmaceuticals, said in a company-issued press release. “We will conduct additional analyses — together with our partner, Celgene — to understand these outcomes.
“We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned,” Hastings added. “OncoMed remains focused on completing and analyzing the results of the two randomized phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year, and in continuing the advancement of our portfolio of biotherapeutic candidates.”
The combination of demcizumab and chemotherapy appeared well tolerated. The most common toxicities were nausea, diarrhea, anemia and fatigue. The most common grade 3 or higher adverse events in demcizumab-treated patients were heart failure (3.7% for demcizumab vs. 0% for placebo), pulmonary hypertension (0.7% vs 0%) and bleeding (8.1% vs. 1.5%).
“Pancreatic cancer has proven to be a uniquely challenging disease, and these data appear to reflect some of those disease and treatment complexities,” Robert Stagg, PharmD, senior vice president of clinical research and development at OncoMed Pharmaceuticals, said in the release. “The safety data seen in the YOSEMITE trial were generally consistent and in line with our expectations. We continue to analyze these data, and look forward to presenting the full study findings at a future scientific congress.”