Merck’s bid to bump Bristol’s Yervoy succeeds


Merck & Co could not have hoped for a better outcome from Keynote-598, a trial that asked whether giving Bristol Myers Squibb’s anti-CTLA-4 MAb, Yervoy, on top of Merck’s Keytruda in first-line NSCLC would add anything. No, is the answer, apart from additional toxicities: the trial was stopped for futility and patients advised to discontinue Yervoy. Merck will have been motivated to design the trial with this outcome in mind; however, this is embarrassing for Bristol, which really only has itself to blame. Its own pivotal lung cancer trials made it very hard to determine whether Yervoy adds anything to PD-1 blockade. Still, it is already widely appreciated that Yervoy is toxic, albeit targeting a checkpoint that holds great potential in fighting cancer. This is why CTLA-4 continues to be explored by many developers seeking improved tolerability – including Merck, whose quavonlimab is in an extensive mid-stage programme. A further question is where Yervoy goes now. Opdivo plus Yervoy is approved in first-line lung, getting the go-ahead in Europe only last week. But for physicians trying to choose between this combo or Keytruda +/- chemo, the decision surely just got easier.

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