Merck Initiates Phase 3 KANDLELIT-007 Trial Of Calderasib Plus KEYTRUDA QLEX In KRAS G12C NSCLC

Merck, known as MSD outside the United States and Canada, announced the initiation of KANDLELIT-007, a Phase 3 clinical trial evaluating calderasib (MK-1084), an investigational oral selective KRAS G12C inhibitor, in combination with KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) as first-line treatment for patients with KRAS G12C-mutant advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).

KANDLELIT-007 (NCT07190248) is a randomized, open-label, multicenter study designed to compare once-daily oral calderasib plus subcutaneous KEYTRUDA QLEX with KEYTRUDA QLEX combined with pemetrexed and platinum-based chemotherapy (carboplatin or cisplatin). In both arms, KEYTRUDA QLEX will be administered once every six weeks. In the comparator arm, pemetrexed will be administered on days 1 and 22 of each three-week cycle, while platinum chemotherapy will be given for up to two cycles.

“While outcomes for patients with NSCLC have significantly improved over the last decade, we know there is more work to do. KRAS is the most frequently mutated oncogene in cancer, and the KRAS G12C mutation occurs in approximately 4% to 14% of all patients with lung cancer globally,” said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck Research Laboratories. “By pairing our oral calderasib candidate with subcutaneously administered KEYTRUDA QLEX in this trial, we will evaluate whether this chemotherapy-free combination that requires no intravenous access may help improve outcomes for patients with KRAS G12C-mutant NSCLC.”

The trial plans to enroll approximately 675 patients worldwide. The primary endpoint is progression-free survival (PFS) in patients whose tumors express PD-L1 (tumor proportion score ≥1%). Secondary endpoints include PFS in the overall study population, overall survival, overall response rate, duration of response, and safety across both PD-L1–expressing patients and all enrolled participants.

In addition to KANDLELIT-007, calderasib is being evaluated across a broad late-stage clinical development program. This includes the Phase 3 KANDLELIT-012 study in combination with cetuximab and mFOLFOX6 for first-line treatment of KRAS G12C-mutant colorectal cancer, and the Phase 3 KANDLELIT-004 study assessing calderasib with KEYTRUDA in patients with high PD-L1–expressing KRAS G12C-mutant NSCLC. Calderasib is also under investigation in the Phase 1 KANDLELIT-001 and Phase 2 KANDLELIT-014 studies across multiple KRAS G12C-mutant solid tumors, both as monotherapy and in combination regimens. Data from KANDLELIT-001 were presented at the 2025 ESMO Congress.

Calderasib is being developed through a strategic collaboration with Taiho Pharmaceutical Co., Ltd. and Astex Pharmaceuticals, a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd., established in January 2020.