On January 7, 2026, Merck announced the initiation of the global Phase 3 KANDLELIT-007 trial (NCT07190248), a randomized, open-label, multicenter study evaluating calderasib (MK-1084), an investigational once-daily oral selective covalent inhibitor of KRAS G12C, in combination with KEYTRUDA QLEX™ as first-line therapy for adults with newly diagnosed advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) harboring KRAS G12C mutations.
The trial enrolls approximately 675 patients and compares the experimental arm—oral calderasib plus subcutaneous KEYTRUDA QLEX (a fixed-dose combination of pembrolizumab, a PD-1 inhibitor, and berahyaluronidase alfa for enhanced subcutaneous delivery, administered every six weeks)—against the control arm of KEYTRUDA QLEX plus intravenous pemetrexed and platinum chemotherapy (carboplatin or cisplatin). This design evaluates a potentially chemotherapy-free regimen requiring no intravenous access, offering greater convenience.
The primary endpoint is progression-free survival (PFS) assessed by blinded independent central review in patients with PD-L1 tumor proportion score (TPS) ≥1%. Key secondary endpoints include PFS in all patients, overall survival, objective response rate, duration of response, and safety across subgroups. KRAS mutations are the most common oncogenic drivers in cancer, with the G12C variant occurring in 4%-14% of NSCLC cases globally, predominantly in adenocarcinomas. Historically challenging to target, KRAS G12C inhibitors represent a therapeutic advance. The combination rationale builds on calderasib’s mechanism and prior data from the KANDLELIT program, including Phase 1/2 studies showing manageable safety and antitumor activity as monotherapy or with pembrolizumab.
Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories, stated that pairing calderasib with subcutaneous KEYTRUDA QLEX could improve outcomes for this patient population while addressing administration burdens. Lung cancer remains the leading cause of cancer mortality worldwide. This trial addresses unmet needs in KRAS G12C-mutant NSCLC, potentially establishing a novel standard for first-line treatment. Calderasib originates from a collaboration with Taiho Pharmaceutical and Astex Pharmaceuticals. Forward-looking statements highlight risks, including clinical, regulatory, and competitive uncertainties.
