Third Phase 3 trial in Merck’s KANDLELIT clinical development program, which is investigating calderasib in KRAS G12C-mutant cancers across multiple tumor types and treatment settings
January 7, 2026 --RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today 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) for the first-line treatment of patients with KRAS G12C-mutant, advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).
This randomized, unblinded open-label, multicenter clinical trial (NCT07190248) will evaluate calderasib given orally once daily in combination with KEYTRUDA QLEX administered subcutaneously, compared with subcutaneous KEYTRUDA QLEX in combination with intravenous pemetrexed and chemotherapy (carboplatin or cisplatin), in newly diagnosed patients with KRAS G12C-mutant advanced or metastatic nonsquamous NSCLC. In both treatment arms, KEYTRUDA QLEX will be administered once every six weeks; in the comparator arm, pemetrexed will be given on days 1 and 22 of every three-week cycle and carboplatin or cisplatin will be given on days 1 and 22 for up to two three-week 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 will enroll approximately 675 patients globally. The primary endpoint of the study is progression-free survival (PFS) in patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%). Secondary endpoints include PFS in all study participants and overall survival, overall response rate, duration of response and safety in both the PD-L1 (TPS ≥1%) expressor patient population and all comers.
In addition to KANDLELIT-007, calderasib is being investigated in the Phase 3 KANDLELIT-012 study (NCT06997497), which is evaluating calderasib in combination with cetuximab and mFOLFOX6 for the first-line treatment of certain patients with KRAS G12C-mutant locally advanced unresectable or metastatic colorectal cancer, and the Phase 3 KANDLELIT-004 study (NCT06345729), which is investigating calderasib in combination with KEYTRUDA ® (pembrolizumab) for the first-line treatment of certain patients with KRAS G12C-mutant locally advanced or metastatic NSCLC whose tumors express PD-L1 (TPS ≥50%). Calderasib is also currently being evaluated in the Phase 1 KANDLELIT-001 trial (NCT05067283) to assess safety, tolerability, pharmacokinetics and efficacy of calderasib as monotherapy and as part of various combination therapies in patients with KRAS G12C-mutant advanced solid tumors and in the Phase 2 KANDLELIT-014 study (NCT07209111) evaluating calderasib as monotherapy and in combination with cetuximab for certain patients with KRAS G12C-mutant advanced solid tumors. As announced, data from KANDLELIT-001 were presented at the 2025 European Society for Medical Oncology Congress.
Calderasib is being developed through a collaboration with Taiho Pharmaceutical Co. Ltd. and Astex Pharmaceuticals (UK), a wholly owned subsidiary of Otsuka Pharmaceutical Co., Ltd. This collaboration was announced in January 2020.
About calderasib
Calderasib (MK-1084) is an investigational, potent and specific KRAS G12C covalent inhibitor. Mutations in KRAS are among the most prevalent mutations found in cancer, occurring with high frequency in non-small cell lung cancer, pancreatic, urogenital and colorectal cancers. The KRAS G12C mutation is the most frequently observed KRAS mutation in patients, occurring in approximately 4% to 14% of patients with non-small cell lung cancer (adenocarcinoma) depending on their geographic location. Despite decades of research and recognition of the therapeutic importance of targeting KRAS, the development of small molecule inhibitors targeting KRAS mutations has been challenging.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% of all cases. Early detection and screening remain an important unmet need, as 43% of lung cancer cases are not found until they are advanced.
About KEYTRUDA® (pembrolizumab) injection for intravenous use, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
About KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) injection for subcutaneous use, 165 mg + 2,000 units/mL
KEYTRUDA QLEX is a fixed-combination drug product of pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody and berahyaluronidase alfa enhances dispersion and permeability to enable subcutaneous administration of pembrolizumab. KEYTRUDA QLEX is administered as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel, over one minute every three weeks (2.4 mL) or over two minutes every six weeks (4.8 mL).
Merck’s focus on cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities.