Merck Launches Phase 3 KANDLELIT-007 Trial in KRAS G12C NSCLC

Merck & Co. has initiated KANDLELIT-007, a global Phase 3 clinical trial evaluating its investigational oral KRAS G12C inhibitor calderasib (MK-1084) in combination with KEYTRUDA QLEX™, a subcutaneous formulation of pembrolizumab with berahyaluronidase alfa-pmph. The study targets the first-line treatment of patients with advanced or metastatic KRAS G12C-mutant nonsquamous non-small cell lung cancer (NSCLC).

The randomized, open-label, multicenter trial plans to enroll around 675 patients worldwide. Eligible participants are newly diagnosed with advanced disease and have not received prior systemic therapy for metastatic non-small cell lung cancer. Patients will be randomized to receive either calderasib plus KEYTRUDA QLEX, or KEYTRUDA QLEX in combination with standard platinum-based chemotherapy, including pemetrexed with either carboplatin or cisplatin.

KRAS G12C mutations are present in a significant subset of NSCLC patients and have long been associated with limited targeted treatment options. While KRAS inhibitors have shown activity in previously treated patients, outcomes in the first-line setting remain an area of active investigation. Merck’s study aims to assess whether combining calderasib with immunotherapy can improve disease control without the use of chemotherapy.

The primary endpoint of KANDLELIT-007 is progression-free survival (PFS) in patients whose tumors have a PD-L1 tumor proportion score of at least 1 %. Key secondary endpoints include progression-free survival in the overall study population, overall survival, objective response rate, duration of response, and safety and tolerability.

According to Merck, the trial reflects its broader oncology drug development strategy of advancing targeted therapies alongside established immuno-oncology agents. In addition to KANDLELIT-007, calderasib is being evaluated in other late-stage studies, including trials in colorectal cancer and additional NSCLC settings.

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If successful, the study could support a new first-line NSCLC treatment option for patients with KRAS G12C-mutant disease, a group with ongoing unmet clinical needs.