Bristol-Myers details its failure on Checkmate 451, highlighting a bleak future for their checkpoint combo
We found out last fall that Bristol-Myers Squibb’s combination of its PD-1/CTLA-4 drugs Opdivo and Yervoy failed to work as a maintenance therapy for small cell lung cancer. Today, we got the details. And it wasn’t pretty.
Researchers enrolled 834 patients in Checkmate 451 to see if delivering the combo after successful chemo would help prevent the cancer from coming back.
As we saw from a blast of tweets from oncologists at the European Lung Cancer Congress, the overall survival rate for the patients in the combo arm was 9.2 months, compared to a slightly longer 9.6 months for the placebo group.
The hazard ration was an abysmal 0.92.
— Antonio Passaro MD PhD (@APassaroMD) April 11, 2019
Bristol-Myers Squibb has already taken its hit on the trial failure, which raised serious doubts that PD-1/L1 combined with CTLA-4 can benefit patients or the company to a significant extent. AstraZeneca has had its own setbacks in the same field with its in-house drugs. This new data will only underscore the bleak future the combo has in the cancer field.
Study author Taofeek Owonikoko, an Emory professor, called the results “a big disappointment,” but believes the study provided one new pathway to explore.
There was some indication that compared to placebo, it took longer for the cancer to progress in patients who received either combination immunotherapy or nivolumab alone. This was not the primary endpoint of the study so we cannot make definitive conclusions, but it shows that this strategy could be promising, especially in patients who are responsive to immunotherapy. The challenge will be how to select and identify those patients since patients who began maintenance therapy sooner after completion of chemotherapy did appear to derive greater benefit.
Bristol-Myers’ failure to maintain the lead in the PD-1/L1 field, watching Merck surge to the lead, no doubt helped inspire its big Celgene buyout.