Bristol-Myers Squibb has lost yet more ground in its ongoing cancer immunotherapy battle with rival Merck.
Along with its earnings, the pharma firm reported Thursday that it has pulled a key approval application to use a combo regimen of its already approved immunotherapies, nivolumab (Opdivo) and ipilimumab (Yervoy), in a portion of patients with newly diagnosed, advanced non-small cell lung cancer (NSCLC).
Specifically, Bristol (NYSE: BMY) said that, upon discussions with the FDA, it needs more data to support the approval filing. The problem: Bristol needs to provide additional evidence for “the relationship between [tumor mutational burden] and PD-L1”—two biomarkers meant to help identify patients who might respond to immunotherapy—to really tell if the Bristol regimen is helping patients live longer.
To get that information, Bristol needs more results from the large, ongoing Phase 3 study called Checkmate-227. Those results are expected in the first half of this year, but that’s too late under the current review cycle for the ipi-nivo application, which ends on May 20. As a result, Bristol will have to re-file the application afterwards.
Bristol shares fell about 3.6 percent in pre-market trading on Thursday.
The results are another setback for Bristol in lung cancer, and they’re emblematic of the uncertainty surrounding the use of TMB—a measure of the levels of genetic mutations within a tumor—as an effective biomarker for cancer immunotherapy.
In October 2015, the FDA approved nivolumab and the Merck (NYSE: MRK) immunotherapy pembrolizumab (Keytruda) within days of one another for patients whose NSCLC had spread after chemotherapy. But a year later, pembrolizumab succeeded in a Phase 3 trial in newly diagnosed advanced NSCLC patients and nivolumab failed.
Since then, Merck has blown past Bristol. Pembrolizumab became the first FDA-approved immunotherapy for NSCLC patients, and Merck followed with an FDA approval of pembrolizumab plus chemotherapy in newly diagnosed patients. Roche, too, has nabbed an approval of an immunotherapy combination in first-line NSCLC. Bristol has banked on a combo of nivolumab and ipilimumab to bounce back. To do so, it has zeroed in on TMB, an emerging marker that, at least as of yet, hasn’t been used to support an FDA approval of an immunotherapy. (Measuring the abundance of the protein PD-L1 on a patient’s tumor, by comparison, is currently a more established, albeit imperfect, immunotherapy biomarker.)
In Checkmate-227, Bristol reported in April 2018 that patients with “high” TMB—which Bristol defined as patients with TMB of 10 mutations per megabase or greater—on ipi-nivo saw their tumors held in check longer than those on chemotherapy. The company has been using those results to seek approval of ipi-nivo for a slice of non-small cell lung cancer patients. But as experts told Xconomy last April, there isn’t yet a consensus about what TMB is or the best way to use it. Now the FDA wants a closer look.