Merck shoots for KRAS all comers
The Kandlelit-007 trial will assess MK-1084 plus SC Keytruda across PD-L1 expression levels.
The Kandlelit-007 trial will assess MK-1084 plus SC Keytruda across PD-L1 expression levels.
Merck & Co already has a phase 3 trial under way with its KRAS G12C inhibitor MK-1084 in PD-L1-high first-line lung cancer, and now it’s aiming at all comers. The Kandlelit-007 trial, just listed on clinicaltrials.gov and set to start in October, is also notable for combining MK-1084 with subcutaneous Keytruda, recently FDA approved as Keytruda Qlex.
Kandlelit-007 will compare this combo versus Keytruda plus chemo, with a primary endpoint of progression-free survival. However, this is limited to patients with PD-L1 expression of 1% or higher; PFS in all comers is a secondary endpoint.
A look at other KRAS G12C inhibitor players show different groups taking varying approaches in first-line NSCLC. Amgen, for example, has focused on PD-L1 negatives with a Lumakras/chemo combo, a decision likely spurred by liver enzyme elevations with Lumakras plus PD-(L)1 inhibitors in a mostly pretreated patient population.
Meanwhile, Roche is focused solely on all comers with the Krascendo-2 trial of its contender divarasib. That study looks to have been delayed: its start date on ct.gov was previously given as May 2025, but is now December 2025.
Early
Roche recently disclosed plans to go even earlier with divarasib, into the adjuvant setting; Lilly is the only other player to have ventured here so far.
Both Lilly and Bristol Myers Squibb are separately assessing PD-L1-high patients and all comers with their G12C inhibitors, olomorasib and Krazati respectively. But, unlike Merck, both of those groups have plumped for a combo with Keytruda and chemo in the all-comers population.
It could be a while before it becomes clear which approach is best. Lilly’s olomorasib could be the first of the Keytruda combos to yield data, with the Sunray-01 trial set to complete next year.
Another contender could be Revolution Medicines, which has said it plans to start “one or more pivotal combination trials” next year incorporating either its G12C-selective elironrasib, or its G12D-selective zoldonrasib.
Western phase 3 studies of KRAS G12C inhibitors in 1st-line NSCLC
| Trial | Setting | Regimen | Primary endpoint | Note |
|---|---|---|---|---|
| MK-1084 (Merck & Co) | ||||
| Kandlelit-004 | PD-L1 ≥50% | + IV Keytruda, vs IV Keytruda | PFS, OS | Completes Feb 2029 |
| Kandlelit-007 | PD-L1 all-comers | + SC Keytruda, vs SC Keytruda + chemo | PFS in PD-L1 ≥1% | To start 27 Oct 2025 |
| Lumakras (Amgen) | ||||
| Codebreak-202 | PD-L1-negative | + chemo, vs Keytruda + chemo | PFS, OS | Completes Jun 2026 |
| Olomorasib (Lilly) | ||||
| Sunray-01 | PD-L1 ≥50% | + Keytruda, vs Keytruda | PFS | Completes Oct 2026 |
| PD-L1 all comers | + Keytruda + chemo, vs Keytruda + chemo | PFS | ||
| Krazati (Bristol Myers Squibb) | ||||
| Krystal-7 | Ph3 portion: PD-L1 ≥50% | + Keytruda, vs Keytruda | PFS, OS | Data due 2028 |
| Krystal-4 | PD-L1 all comers | + Keytruda + chemo, vs Keytruda + chemo | PFS, OS | Data due 2029 |
| Divarasib (Roche) | ||||
| Krascendo-2 | PD-L1 all comers | + Keytruda, vs Keytruda + chemo | PFS, OS | To begin Dec 2025 (prev May 2025) |
Source: OncologyPipeline & clinicaltrials.gov.
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