The Eagle does not fly for Astra

Last week’s failure of Imfinzi’s Eagle study in head and neck cancer is neither the first for a checkpoint blocker nor for Astrazeneca’s anti-PD-L1 drug in particular. Trials of Imfinzi had been put on clinical hold back in 2016 after bleeding events were seen, though this was lifted within a month. And Merck & Co’s Keytruda failed its Keynote-040 study, which like Eagle was in the second-line setting. However, Keytruda had the advantage of already having secured accelerated approval in head and neck cancer, and after hailing the front-line Keynote-048 study a success Merck moved swiftly to withdrawing its filing and seeking a formal first-line label (Esmo 2018 – Merck & Co’s head (and neck) scratcher, October 22, 2018). Astra’s own front-line head and neck cancer study, Kestrel, could still read out this year. Either way, it is clear that checkpoint blockers are not a panacea for all cancers, and some malignancies are proving particularly tough to crack. While Opdivo leads the checkpoint inhibitors with four broken trials to its name, it should be noted that failure in NSCLC could be a combination of poor study design and a fast-changing competitive landscape.

Failed studies of anti-PD-(L)1 antibodies across various cancer types
  Urothelial Gastric Glioblastoma NSCLC SCLC Head & neck
Keytruda (Merck & Co)   Keynote-061 (2L)       Keynote-040 (2L)
Opdivo (Bristol-Myers Squibb)     Checkmate-143 (2L) Checkmate-026 (1L) Checkmate-331 (2L)
Checkmate-451 (1L)*
Tecentriq (Roche) Imvigor-211 (2L)*          
Imfinzi (Astrazeneca)       Mystic (1L)*   Eagle (2L)*
Bavencio (Merck KGaA/Pfizer)       Javelin Lung 200 (2L)    
*CTLA-4 combo; 1L=1st line; 2L=2nd line.

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