Pfizer's Bavencio flops third key study, this time in lung cancer. Can crossover really explain it?

Pfizer and Merck KGaA have suffered another setback with immuno-oncology med Bavencio—and this one’s raising some eyebrows.

Thursday, the companies said Bavencio (avelumab) had failed to outdo chemo at extending the lives of second-line lung cancer patients with PD-L1-positive tumors. And the way Evercore ISI analyst Umer Raffat sees it, there’s no “good reason” to explain the flop.

“The news today on Pfizer’s 2L lung failure marks the first time we can start to say that PFE may have underperformed,” he wrote to clients Thursday.

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Pfizer and Merck KGaA have already come up short in two other key trials—one testing Bavencio in a range of solid tumors alongside an immuno-oncology candidate dubbed “4-1BB,” and one in third-line gastric cancer. But Raffat, for one, credits the first trial’s misfire to 4-1BB rather than to Bavencio. And “on gastric failure, PFE should get a pass ... mostly because PFE’s 3L gastric trial was vs. chemo,” whereas Bristol-Myers Squibb and Merck, which succeeded in their own gastric trials, put their meds up against placebo, he wrote.

In regards to the latest misstep, Pfizer and Merck KGaA were quick to point to a high crossover rate from the chemo arm to the Bavencio arm, noting that the proportion of patients “was higher than previously reported in post-platinum immunotherapy clinical trials.” But Raffat wasn’t convinced.

“I hear Pfizer’s point, but I don’t buy it entirely,” he wrote, pointing out that Merck “had 15% crossover and yet clearly hit” in its own trial of previously treated lung cancer patients.

That’s not to say the trial brought all bad news for the drugmakers. Lead investigator Fabrice Barlesi maintained in a statement that Bavencio “performed in line with expectations in the trial,” and the companies highlighted improvements in survival among patients with higher levels of PD-L1 expression.

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Meanwhile, with each slip-up for Bavencio, attention to turns to Pfizer—and whether the deal-hungry giant will stick with the partnership or look to snap up a competitor. Industry watchers have speculated the New York behemoth may have its eye on a buyout of an immuno-oncology leader such as Bristol-Myers Squibb or AstraZeneca—particularly if stumbles for those companies force down the price of shares.

For now, though, Pfizer's stressing its plans to stay the Bavencio course. As Bernstein's Tim Anderson, who has grilled Pfizer execs extensively on the potential of jumping ship, wrote in his own note to clients Thursday, it "seems odd to us" that Pfizer didn't participate in a conference call on the trial. But "in the companies' joint press release, there was an explicit comment from PFE's head of IO saying how it will continue to pursue a broad program with avelumab," he added.