Bristol-Myers Squibb has withdrawn its application to the European Medicine Agency (EMA) requesting the use of Opdivo (nivolumab) plus Yervoy (ipilimumab) combination therapy as a first-line treatment for people with advanced non-small cell lung cancer (NSCLC).
Based on results from the CheckMate-227 Phase 3 clinical trial (NCT02477826), the application was filed originally in 2018 and was intended for NSCLC patients with highly mutated tumors. It was revised to include overall survival data of patients with tumors positive for the marker PD-L1, the protein target of Opdivo.
The Committee for Medicinal Products for Human Use, an arm of the EMA, recognized the integrity of patient data, but argued that a full assessment of the Opdivo-Yervoy application was not possible given the multiple changes made in the trial protocol by Bristol-Myers Squibb.
CheckMate-227 evaluated the safety and effectiveness of Opdivo-Yervoy versus chemotherapy in 1,700 patients with advanced NSCLC who had not received prior treatment. It included two primary efficacy measures, or endpoints: overall survival of patients with PD-L1-positive tumors; and survival without disease progression in patients with highly mutated tumors (tumor mutational burden of 10 or more mutations per megabase of DNA), regardless of PD-L1 status.
Both primary goals were met. “Opdivo plus Yervoy demonstrated a statistically and clinically significant overall survival benefit compared to chemotherapy for patients with first-line NSCLC. The durable survival benefit seen in CheckMate-227 is an important result for patients and we are disappointed with the CHMP’s position,” Samit Hirawat, MD, Bristol-Myers Squibb’s chief medical officer, said in a press release.
The company has a similar application under priority review by the U.S. Food and Drug Administration, with a final decision expected in May.
Bristol-Myers Squibb said it has no plans to refile the application in the European Union, but intends to submit new requests for Opdivo-Yervoy combined with chemotherapy in the U.S., Europe, and elsewhere, based on positive preliminary results of CheckMate-9LA (NCT03215706).
The trial, which is recruiting at more than 130 locations, is evaluating Opdivo plus Yervoy combined with a shorter course of chemotherapy for the initial treatment of advanced NSCLC.
“Patients with lung cancer should have access to innovative new therapies that offer the promise of long-term overall survival. We are continuing to advance our application in the U.S. for CheckMate-227 and plan to file data from CheckMate-9LA in markets globally to help address the serious unmet need in first-line lung cancer,” Hirawat said.
Opdivo and Yervoy — both sold by Bristol-Myers Squibb — are immunotherapies belonging to the class of immune checkpoint inhibitors. Both are antibodies and target different proteins involved in the mechanisms used by cancer cells to escape the immune system. Opdivo targets the PD-L1 protein on cancer cells, and Yervoy targets the CTLA-4 protein on T-cells, which are immune cells with the ability to fight tumors.
