Results

Trading places with Bristol-Myers, Merck hit with another late-stage setback on checkpoint star Keytruda

Close to a year after Merck $MRK won an accelerated FDA OK to use its PD-1 checkpoint star Keytruda for treating second-line cases head and neck squamous cell carcinoma in combination with platinum-containing chemo, the pharma giant announced that its big Phase III study for that indication failed.

The pivotal KEYNOTE-040 trial failed to meet the primary endpoint on overall survival in comparing the blockbuster checkpoint against standard therapies, the pharma giant reported. But the current approval stands nevertheless, Merck said in a statement.

“The company noted that the FDA remains comfortable with the drug’s current accelerated approval in this indication despite the trial results,” observed Leerink’s Seamus Fernandez. “Importantly, Keytruda appears to have another shot on goal for full approval in H&N cancer, as the Keynote-048 study in first-line patients could, if positive, serve as the confirmatory trial.”

Roger Perlmutter, Merck

Merck didn’t provide a lot of details, but this is the latest in a series of setbacks in the field that have begun to show the outer limits of efficacy for a new class of cancer med that has transformed oncology therapy in the past two years. But right now, those outer limits of efficacy run along a blurry line, with no clear explanations for what is causing these sudden breakdowns.

Merck recently was forced to put a slate of 3 Keytruda trials for multiple myeloma on hold after investigators spotted a higher rate of death in the checkpoint arm. Two of those studies used combinations with Celgene drugs, Pomalyst and its big drug Revlimid.

Merck has initiated hundreds of studies, including some 300 combination studies, as it races to capitalize on its new lead in the field after Bristol-Myers Squibb ran into serious issues with a failed study for lung cancer. It’s clear that after seeing some remarkable improvements for a significant minority of checkpoint patients, these therapies have their limits. Roche has also had its own problems with the failure of a Phase III confirmatory study using Tecentriq.

Bristol-Myers’ Opdivo, meanwhile, posted positive Phase III data on squamous cell carcinoma of the head and neck back in late 2016, with a median OS of 7.5 months for Opdivo compared to 5.1 months for investigator’s choice.

What to make of that?

“Up until yesterday,” noted Evercore ISI’s Umer Raffat, “I would have told you that there are at least 2 different indications where MRK worked and others failed … and perhaps MRK is just executing these trials much better.  However, as of today, there appears to be no consistency in the inconsistency.  Now MRK failed where BMY worked.”

“We are encouraged by the positive impact that KEYTRUDA has had on many cancer patients, including those with previously treated recurrent or metastatic head and neck cancer, and we remain confident that KEYTRUDA is an important therapy for this difficult-to-treat cancer,” said Roger Dansey, late-stage oncology development leader, Merck Research Laboratories. “We look forward to sharing the comprehensive data analysis from KEYNOTE-040 with the scientific community at an upcoming medical meeting.”


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