It might come as a surprise that Merck & Co is developing a Yervoy competitor, but the group’s own CTLA-4 inhibitor, now called quavonlimab, is an important asset. At last week’s IASLC North America conference a phase I first-line NSCLC study of quavonlimab plus Keytruda was at last updated, showing a handful more subjects versus what had been disclosed at Esmo 2018, but importantly revealing survival data too. Of course this trial had no Keytruda-only cohort, so the only logical comparison is versus Keynote-042, which backs the monotherapy’s US approval in front-line NSCLC patients expressing PD-L1 at ≥1%. While the latter cites median OS of 16.7 months in these PD-L1 expressers, the quavonlimab combo has now shown 18.1 months in all-comers at its phase II target dose of 25mg every six weeks – albeit at the expense of 30% of patients reporting treatment-related adverse events. It is now essential to watch the Keynote-598 trial, ending in February 2023 and testing Keytruda plus Yervoy versus Keytruda in first-line NSCLC. Merck stands to win both ways: if Yervoy shows no added benefit a competitor has been beaten, but if it does Merck has quavonlimab waiting in the wings.
|Summary of key quavonlimab (MK-1308) data in 1st-line NSCLC|
|PD-L1 ≥1%||PD-L1 <1%|
|Keytruda + quavonlimab 25mg q6wk* (n=40)||38% ORR|
|Keytruda combo with all 4 quavonlimab doses** (n=134)||39% ORR||33% ORR|
|Keytruda monotherapy in Keynote-042 (n=637)||27% ORR||NA|
|Note: *recommended ph2 quavonlimab dose, ORR at Esmo 2018 was 36% (13/36); **ORR at Esmo 2018 was 31% (33/105). Source: IASLC, Esmo & Keytruda US label.|