Merck, known as MSD outside the US and Canada, has begun the global Phase 3 KANDLELIT-007 clinical trial to evaluate Calderasib (MK-1084), an investigational oral KRAS G12C inhibitor, in combination with KEYTRUDA QLEX for the first-line treatment of patients with KRAS G12C-mutant advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).
The randomized, open-label, multicenter study (NCT07190248) will enroll about 675 patients worldwide. It will compare once-daily oral calderasib plus subcutaneous KEYTRUDA QLEX with the current standard regimen of KEYTRUDA QLEX combined with pemetrexed and platinum chemotherapy (carboplatin or cisplatin). KEYTRUDA QLEX will be administered once every six weeks in both arms.
The primary endpoint is progression-free survival (PFS) in patients whose tumours express PD-L1 (TPS ≥1%). Secondary endpoints include PFS in all participants, overall survival, overall response rate, duration of response and safety.
Calderasib is also being studied in multiple late-stage programmes, including KANDLELIT-012 in KRAS G12C-mutant colorectal cancer, KANDLELIT-004 in PD-L1-high KRAS G12C-mutant NSCLC, and earlier-stage studies assessing the drug alone and in combinations. Development of calderasib is being carried out through a collaboration with Taiho Pharmaceutical and Astex Pharmaceuticals, a subsidiary of Otsuka Pharmaceutical.
KRAS G12C mutations occur in roughly 4% to 14% of NSCLC cases globally, making it one of the most common oncogenic drivers in lung cancer. NSCLC accounts for about 80% of all lung cancers, which remain the leading cause of cancer-related deaths worldwide.
KEYTRUDA QLEX is a subcutaneous formulation of pembrolizumab combined with berahyaluronidase alfa, designed to enable rapid injection while maintaining the clinical profile of intravenous KEYTRUDA. Both KEYTRUDA and KEYTRUDA QLEX are already approved across multiple NSCLC indications, including first-line use with chemotherapy and as monotherapy in PD-L1-positive disease.
Merck continues to expand its immuno-oncology programme, with more than 1,600 KEYTRUDA trials underway across cancer types, as it advances combination and targeted strategies aimed at improving outcomes for lung cancer patients.
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