RE:RE:G12C/G12V KRAS mutation in PC & CRC patients respond to PelaApril 03, 2024 - Madeleine Armstrong - Merck (MSD) makes haste to catch up in KRAS " Merck & Co might be a latecomer to KRAS inhibition, but it clearly wants to make up for lost time. Less than six months after reporting first human data, the group has moved its G12C inhibitor MK-1084 into a phase 3 trial in first-line non-small cell lung cancer.
The move sets up the prospect of another duel between Merck and its checkpoint inhibitor rival Bristol Myers Squibb, whose Mirati-originated Krazati is already in phase 3 here. Both groups are evaluating Keytruda combinations in PD-L1-high patients.
Meanwhile, the other big KRAS contender, Amgen, is now focused on a Lumakras/chemo combo in first-line NSCLC patients negative for PD-L1. That group saw liver enzyme elevations when it tested its therapy alongside PD-(L)1 inhibitors in a mostly pretreated patient population.
Better than Krazati?
Merck’s early data, presented at last year’s ESMO, suggested that a MK-1084/Keytruda combo might have an edge over a Krazati plus Keytruda – although there are plenty of reasons to be cautious, including the small number of patients in Merck’s trial and the fact that neither study was controlled.
Things should become clearer with the readouts of the new Merck pivotal trial and the phase 3 portion of the Krystal-7 study, but these are a while away. Bristol said in February that data were expected in 2028, while the MK-1084 pivotal trial completes in early 2029. Both studies are assessing progression-free and overall survival.
Meanwhile, Roche’s divarasib, which burst onto the KRAS scene last year, is behind in first-line lung, with a phase 1/2 study set to yield data this year or next. The Swiss group seems to be focused on second-line disease, where Lumakras and Krazati already have accelerated approvals. Still, Roche isn’t expecting to file divarasib here until 2026 or later.
This makes Merck’s speed look all the more impressive; but the company will have to hope that in zooming past phase 2 it hasn’t acted rashly."