The supplemental Biologics License Application (sBLA) requesting the extension of Opdivo’s indications to include metastatic colorectal cancer patients who have mismatch repair deficiencies (dMMR) or high microsatellite instability (MSI-H), has been accepted for review by the U.S. Food and Drug Administration (FDA). The application has received priority review status, and a decision is expected by Aug. 2.
“We look forward to working with the FDA toward the goal of providing a new treatment option for patients with metastatic colorectal cancer defined by dMMR or MSI-H biomarkers,” Ian M. Waxman, MD, development lead, Gastrointestinal Oncology, Bristol-Myers Squibb, said in a press release. “These patients have a distinct unmet need, as they are less likely to benefit from conventional chemotherapy and have a shorter overall survival than patients with metastatic colorectal cancer without these biomarkers,” he said.
“This milestone illustrates Bristol-Myers Squibb’s continued efforts to evaluate the potential of immuno-oncology in a broad range of cancers and represents an important advancement in our approach to translational medicine,” Waxman added.
The submission was based on data from the ongoing Phase 2 CheckMate -142 trial (NCT02060188) evaluating Opdivo (nivolumab) in metastatic colorectal cancer patients with dMMR or MSI-H.
Mismatch repair deficiency happens when the proteins responsible for repairing mutations in the DNA are faulty or missing. This leads to microsatellite instability-high tumors, which are defined as those with high mutational load. Nearly 4% of metastatic colorectal cancers (mCRCs) are associated with high microsatellite instability.
As a result of the large number of mutations, dMMR and MSI-H colorectal cancers have an increased load of mutated proteins that can trigger immune responses, and immune infiltration. The Phase 2 trial was designed on the basis that immune checkpoint inhibitors could be used to activate the infiltrated immune cells, and enhance tumor cell killing.
The study enrolled dMMR and MSI-H colorectal cancer patients who had progressed on, or were intolerant to, at least one prior line of therapy. They were dosed with Opdivo every two weeks.
The primary endpoint was investigator-assessed objective response rate (ORR), defined as the percentage of patients whose tumor shrank or disappeared. Secondary endpoint was independent review committee-assessed ORR. Other measures, including safety, progression-free survival (PFS), overall survival (PS), and effectiveness in specific subsets were also assessed.
Data presented in January at the 2017 Gastrointestinal Cancers Symposium revealed findings about 74 patients who received Opdivo every two weeks. The investigator-assessed ORR and disease control rate were 31% and 69%. One year after entering the trial, 48.4% of patients were still alive and disease-free. One-year overall survival was 73.8%. Treatment was well-tolerated with no safety signals.