A combination of Opdivo and Yervoy hit the primary endpoint in NSCLC patients with PD-L1 expression. Opdivo and chemotherapy did not demonstrate efficacy in patients regardless of PD-L1 expression.
Bristol-Myers Squibb’s anticipated Phase III CheckMate-227 trial delivered mixed results for the combination of Opdivo and low-dose Yervoy. The trial hit its co-endpoints in the first part of the trial, but failed in the second part, the company said.
On Monday, BMS announced that part Ia of the Phase III trial met the co-primary endpoint of overall survival in non-squamous non-small cell lung cancer (NSCLC) patients whose tumors express PD-L1. The two-drug combination was being tested as a first-line treatment in that patient population versus chemotherapy. The safety profile of BMS’ two immuno-oncology drugs remained consistent with previous studies and BMS noted that the Part Ia portion of the trial marked the third Phase III trial in which a combination of Opdivo and Yervoy demonstrated overall survival benefits. Opdivo is a PD-1 immune checkpoint inhibitor and Yervoy targets CTLA-4, a protein receptor that regulates the immune system.
Martin Reck, lead investigator of the Part Ia portion of CheckMate-227 said the combination of Opdivo (nivolumab) and Yervoy (ipilimumab)offers NSCLC patients with PD-L1-expressing tumors “the potential for a chemo-sparing regimen” that demonstrates an overall survival benefit as a first-line treatment. Reck, who is a researcher at the Lung Clinic Grosshansdorf in the German Center of Lung Research, said he was also encouraged to “see activity in PD-L1 expressors and non-expressors from the combination treatment.” Full trial results will be presented later.
The Phase Ia portion of CheckMate-227 followed the strong Phase Ib portion which showed the combination treatment demonstrated superior” progression-free survival in advanced non-small cell lung cancer (NSCLC) patients whose tumors have high tumor mutation burden (TMB), regardless of PD-L1 expression.
While the Part Ia portion of the trial was a success, the same was not said for the second part of the trial. Part II of CheckMate-227 did not meet its primary endpoint of overall survival. The second part of the trial assessed Opdivo and chemotherapy versus chemotherapy alone as a first-line treatment for NSCLC patients regardless of PD-L1 expression on their tumors. BMS noted that the median overall survival for the Opdivo and chemo patients was 18.83 months versus 15.57 months for chemo patients. That landmark one-year overall survival was 67.3% versus 59.2%, respectively, the company said. BMS also noted that in an exploratory analysis of patients with first-line squamous NSCLC, the median overall survival was 18.27 months for Opdivo plus chemotherapy vs. 11.96 months for chemotherapy.
Fouad Namouni, head of oncology development at BMS, expressed disappointment with the outcome of the Part 2 portion of the trial. Saying the results were not what was hoped for, Namouni said the “Opdivo plus chemotherapy one-year landmark overall survival in the non-squamous population was consistent with the experimental arms in previously-reported trials of IO/chemotherapy combination regimens.”
BMS plans to present complete data from the trial at a later date.
BMS released the mixed results of the trial ahead of its quarterly earnings report. This morning, the company released its second-quarter report that showed revenue of $6.3 billion, a 10% increase over the same quarter the year before. The revenue was primarily driven by strong sales for Eliquis (apixaban) and Opdivo, as well as a “robust operating performance across the portfolio.” Eliquis saw sales jump 24%, a $392 million increase, and Opdivo sales rose by $196 million, or 12%, the company said.
