Phase 3 Trial of Calderasib Combo Launched in Advanced KRAS G12C-Mutant NSCLC

The phase 3 KANDLELIT-007 trial (NCT07190248) evaluating the KRAS G12C inhibitor calderasib (MK-1084) plus subcutaneous pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex; SC pembrolizumab) has been initiated in patients with advanced non–small cell lung cancer (NSCLC) harboring the KRAS G12C mutation.¹

The global, randomized, open-label trial is assessing the efficacy and safety of the combination vs SC pembrolizumab plus intravenous (IV) pemetrexed and carboplatin or cisplatin chemotherapy in the first-line setting.²

The study intends to enroll approximately 675 patients newly diagnosed with KRAS G12C-mutant, advanced or metastatic nonsquamous NSCLC. To be eligible for participation, patients must have stage IIIB or stage IIIC disease not eligible for curative resection or chemoradiation or stage IV (M1a, M1b, or M1c) disease. If patients are positive for human immunodeficiency virus (HIV), the disease must be well controlled with antiretroviral therapy.

Patients will be randomly assigned to 1 of the 2 treatment arms. Both arms will receive fixed-dose SC pembrolizumab once every 6 weeks along with the respective therapies. Those assigned to the investigational arm will receive once-daily oral calderasib, while those in the comparator arm will be given an IV infusion of pemetrexed on days 1 and 22 of every 3-week cycle and carboplatin or cisplatin on the same days for up to 2 3-week cycles.

Upon treatment, the study will be assessing for the primary end point of progression-free survival (PFS) in patients whose tumors express PD-L1, with a tumor proportion score (TPS) ≥1%. Secondary end points include PFS in all study participants, overall survival, overall response rate, duration of response, and safety in both the PD-L1-expressing subgroup and the overall population.

“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 Gregory Lubiniecki, MD, vice president of Global Clinical Development at Merck Research Laboratories, in a news release.¹ “By pairing our oral calderasib candidate with subcutaneously administered [pembrolizumab] 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.”

About Calderasib

Calderasib is an investigational, orally administered small molecule inhibitor of KRAS G12C, part of a burgeoning family of agents³ that seek to overcome the challenge of treating cancers harboring the highly prevalent KRAS mutation. With potential antineoplastic activity, the agent is designed to selectively inhibit downstream oncogenic signaling pathways that drive tumor cell proliferation.⁴

The KANDLELIT Trials: Additional Studies of Calderasib

Along with KANDLELIT-007, other trials in the KANDLELIT series are investigating calderasib in diverse clinical contexts with the KRAS G12C mutation.

• KANDLELIT-012 (NCT06997497): A phase 3 study evaluating first-line calderasib plus cetuximab and mFOLFOX6 in KRAS G12C-mutant, locally advanced unresectable or metastatic colorectal cancer.
• KANDLELIT-004 (NCT06345729): A phase 3 study evaluating first-line calderasib plus pembrolizumab (Keytruda) in KRAS G12C-mutant, PD-L1–expressing (TPS≥50%), locally advanced or metastatic NSCLC.
• KANDLELIT-001 (NCT05067283): A phase 1 study evaluating calderasib monotherapy and various combination therapies in KRAS G12C-mutant advanced solid tumors.
• KANDLELIT-014 (NCT07209111): A phase 2 study evaluating calderasib monotherapy and in combination with cetuximab for select patients with KRAS G12C-mutant advanced solid tumors.

REFERENCES

1. Merck initiates phase 3 KANDLELIT-007 trial evaluating calderasib (MK-1084), an investigational oral KRAS G12C inhibitor, in combination with KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) in certain patients with advanced NSCLC. News release. Merck. January 7, 2026. Accessed January 7, 2026. https://tinyurl.com/yu873w6y

2. A clinical study of MK-1084 and other treatments for participants with non-small cell lung cancer (MK-1084-007/KANDLELIT-007). ClinicalTrials.gov. Updated January 5, 2026. Accessed January 7, 2026. https://clinicaltrials.gov/study/NCT07190248

3. Dunnett-Kane V, Nicola P, Blackhall F, Lindsay C. Mechanisms of resistance to KRASG12C inhibitors. Cancers (Basel). 2021;13(1):151. Published January 5, 2021. doi:10.3390/cancers13010151

4. National Center for Biotechnology Information. PubChem Compound Summary for CID 156295589, Calderasib. Accessed January 7, 2026. https://tinyurl.com/3tnr8tdx