Merck Launches Phase 3 KANDLELIT-007 Trial for Calderasib-KEYTRUDA QLEX Combination in KRAS G12C-Mutant Lung Cancer
核心洞察
Merck (搜索) has initiated KANDLELIT-007, a Phase 3 trial evaluating calderasib (搜索) (MK-1084) combined with KEYTRUDA QLEX (搜索) for first-line treatment of KRAS G12C (搜索)-mutant nonsquamous non-small cell lung cancer.
The randomized trial will enroll approximately 675 patients globally, comparing the chemotherapy-free oral/subcutaneous combination against standard KEYTRUDA QLEX (搜索) plus chemotherapy.
This marks the third Phase 3 study in Merck (搜索)'s KANDLELIT program investigating calderasib (搜索) across multiple KRAS G12C (搜索)-mutant cancer types and treatment settings.
Merck (搜索) has announced the initiation of KANDLELIT-007, a Phase 3 clinical trial evaluating calderasib (搜索) (MK-1084), an investigational oral selective KRAS G12C (搜索) inhibitor, in combination with KEYTRUDA QLEX (搜索) for the first-line treatment of patients with KRAS G12C-mutant, advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).
Trial Design and Patient Population
The randomized, unblinded open-label, multicenter clinical trial (NCT07190248) will evaluate calderasib (搜索) given orally once daily in combination with KEYTRUDA QLEX (搜索) administered subcutaneously, compared with subcutaneous KEYTRUDA QLEX in combination with intravenous pemetrexed and chemotherapy (carboplatin or cisplatin), in newly diagnosed patients with KRAS G12C (搜索)-mutant advanced or metastatic nonsquamous NSCLC.
In both treatment arms, KEYTRUDA QLEX (搜索) 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.
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 (搜索) (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.
Addressing Unmet Medical Need
"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 (搜索) mutation occurs in approximately 4% to 14% of all patients with lung cancer globally," said Dr. Gregory Lubiniecki, vice president, global clinical development, Merck (搜索) Research Laboratories.
"By pairing our oral calderasib (搜索) candidate with subcutaneously administered KEYTRUDA QLEX (搜索) 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 (搜索)-mutant NSCLC," Lubiniecki added.
Expanding KANDLELIT Development Program
KANDLELIT-007 represents the third Phase 3 trial in Merck (搜索)'s KANDLELIT clinical development program investigating calderasib (搜索) in KRAS G12C (搜索)-mutant cancers across multiple tumor types and treatment settings. The drug is also being evaluated in:
-
KANDLELIT-012 (NCT06997497): Phase 3 study evaluating calderasib (搜索) in combination with cetuximab and mFOLFOX6 for first-line treatment of certain patients with KRAS G12C (搜索)-mutant locally advanced unresectable or metastatic colorectal cancer
-
KANDLELIT-004 (NCT06345729): Phase 3 study investigating calderasib (搜索) in combination with KEYTRUDA for first-line treatment of certain patients with KRAS G12C (搜索)-mutant locally advanced or metastatic NSCLC whose tumors express PD-L1 (搜索) (TPS ≥50%)
-
KANDLELIT-001 (NCT05067283): Phase 1 trial assessing safety, tolerability, pharmacokinetics and efficacy of calderasib (搜索) as monotherapy and as part of various combination therapies in patients with KRAS G12C (搜索)-mutant advanced solid tumors
-
KANDLELIT-014 (NCT07209111): Phase 2 study evaluating calderasib (搜索) as monotherapy and in combination with cetuximab for certain patients with KRAS G12C (搜索)-mutant advanced solid tumors
Data from KANDLELIT-001 were presented at the 2025 European Society for Medical Oncology Congress.
About Calderasib and KRAS G12C
Calderasib (搜索) (MK-1084) is an investigational, potent and specific KRAS G12C (搜索) 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.
Lung Cancer Burden
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.
Development Partnership
Calderasib (搜索) is being developed through a collaboration with Taiho Pharmaceutical (搜索) Co. Ltd. and Astex Pharmaceuticals (搜索) (UK), a wholly owned subsidiary of Otsuka Pharmaceutical (搜索) Co., Ltd. This collaboration was announced in January 2020.