Keytruda’s shocker: a US complete response letter


For Merck & Co’s Keytruda, the immunotherapy golden child that can apparently do no wrong, to get a regulatory knock-back is a rarity. So today’s US complete response letter for its use in combination with Eisai’s Lenvima for first-line liver cancer will come as shock. Still, the move is perfectly rational, even if it does show the US FDA taking an unusually hard line. The point is that on June 2 Roche’s Tecentriq plus Avastin had gained a front-line liver cancer label, based on the Imbrave-150 trial, which showed a 42% reduction in risk of death versus Nexavar. This undermined Merck’s case, because Keytruda had been filed on the basis of remission rates in the Keynote-524 study, which later yielded overall survival data but did not have a control arm (Asco 2020 – after Tecentriq’s liver win the spotlight falls on Merck and Astra, June 2, 2020). Keytruda retains its second-line liver cancer accelerated approval even though it failed a confirmatory trial, and Merck’s first-line hopes now rest on the Leap-002 trial, which pits Keytruda plus Lenvima versus Lenvima alone, and ends in 2022.

Immunotherapy in front-line hepatocellular carcinoma
Company Product Clinical trial detail
Roche Tecentriq + Avastin Approved: HR for OS 0.58 (p=0.0006) vs Nexavar in Imbrave-150 study
Merck & Co Keytruda + Lenvima CRL based on Keynote-524 study: mOS 22.0mth, 36% ORR Leap-002 study vs Lenvima ends 2022
Astrazeneca Imfinzi +/- tremelimumab Himalaya study vs Nexavar ends 2020
Bristol Myers Squibb Opdivo Failed Checkmate-459 study vs Nexavar
Source: company presentations.

This story has been corrected to reflect the data on which Keytruda had been filed.

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