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Pfizer, Merck KGaA say their PD-L1 Bavencio also flunked PhIII in the all-important lung cancer field

Playing catch-up in the crowded PD-1/L1 field in cancer R&D is proving particularly tough for Merck KGaA and Pfizer $PFE.

The partners reported this morning that their Phase III lung cancer study JAVELIN Lung 200 failed the primary endpoint for overall survival comparing Bavencio (the PD-L1 avelumab) against docetaxel in second-line lung cancer, a major field for all the players in this particular field.

Researchers swiftly fingered the crossover of patients to other available checkpoints as a likely reason for the flop — raising a threat that may well arise for everyone testing checkpoints in the all-important group of lung cancer patients.

Details are scant as the data will be presented at an upcoming conference, but the partners made sure to provide an explanation:

While the trial did not meet its prespecified endpoint of improving overall survival (OS) in patients with programmed death ligand-1-positive (PD-L1+) (1% or higher) tumors (HR: 0.90 [96% CI: 0.72–1.12], p-value 0.1627, one-sided), the proportion of patients in the chemotherapy arm crossing over to immune checkpoint inhibitors outside the study was higher than previously reported in post-platinum immunotherapy clinical trials, and this may have confounded this trial outcome.

Researchers also pointed to improvements in OS in a sub-group with moderate-to-high and high PD-L1+ expression, as well as lack of new safety concerns, as positive signs. But they face some tough competitors in lung cancer, where Merck has been making headway with Keytruda as Bristol-Myers Squibb and AstraZeneca fight to gain ground. And the companies got some kickback from Evercore ISI’s Uber Raffat: “The news today on Pfizer’s 2L lung failure marks the first time we can start to say that PFE may have underperformed.”

Raffat also questioned if crossovers could really explain the setback, as Merck has reported success before in studies with a 15% crossover rate.

The two big partners won an approval to use their PD-L1 drug against Merkel cell carcinoma, but they’re finding it tough expanding its use to other cancers. Just a couple of months ago they also reported that Bavencio had failed a Phase III study for gastric cancer, putting a crimp in their plans to ramp up sales.

Chris Boshoff

“We are committed to understanding the data in the context of the subpopulations and the impact of access to other immune checkpoint inhibitors,” said Chris Boshoff, a senior vice president and head of immuno-oncology at Pfizer. “We will continue to progress the broad avelumab program, exploring various indications.”


With contribution from John Carroll.


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