Nivolumab Missed Primary Endpoint in NSCLC Trial

August 19, 2016

In a phase III trial, Opdivo (nivolumab) did not meet its primary endpoint, a disappointment to researchers and patients.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and early diagnosis is key for survival. This year, an estimated 224,390 adults (117,920 men and 106,470 women) in the United States will be diagnosed with lung cancer. Patients have been treated with chemotherapy, surgery and radiation, and now immunotherapies are being investigated as alternatives. However, in a recent study they failed to hit the mark.

In a phase III trial, Opdivo (nivolumab) did not meet its primary endpoint, a disappointment to researchers and patients. The CheckMate-026, a trial investigating this monotherapy, failed to meet its primary endpoint of progression-free survival (PFS) in patients with previously untreated advanced NSCLC whose tumors expressed PD-L1 at ≥ 5%. In a previous study, patients receiving nivolumab lived, on average, 3.2 months longer than patients receiving standard chemotherapy. In October 2015, the FDA expanded its approval of nivolumab to include nonsquamous NSCLC.

Designed as a monotherapy to treat NSCLC, nivolumab is a checkpoint inhibitor, which blocks normal proteins on cancer cells, or the proteins on the T cells that respond to them. The Bristol-Myers Squibb researchers are trying to develop an alternative to traditional chemotherapies. Despite this setback, the team will go back and review all aspects of the study to see where modifications could be made for future work in this emerging area of treatment.

Currently, nivolumab is approved for the treatment of BRAF V600 wild-type or mutation-positive unresectable or metastatic melanoma. It is also indicated for treating metastatic NSCLC with progression on or after platinum-based chemotherapy.

Another study, phase III CheckMate-227, explores the potential of the combination of nivolumab plus ipilimumab (Yervoy) for PDL-1 positive patients, and nivolumab plus ipilimumab, or nivolumab plus chemotherapy in PD-L1-negative patients. The team will report results from this when data is available.