Tests calderasib with pembrolizumab in lung cancer with KRAS G12C mutation

Trial details

Who runs it

Merck Sharp & Dohme LLC

Trial code

NCT06345729EU 2023-507776-42-00

Record updated

10 November 2026

Original description

This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There is one primary study hypothesis:Read full original descriptionShow less

A Phase 3, Randomized, Double-blind, Multicenter Study of MK-1084 in Combination With Pembrolizumab Compared With Pembrolizumab Plus Placebo as Firstline Treatment of Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic NSCLC With PD-L1 TPS ≥50% (KANDLELIT-004)

This is a study evaluating the efficacy and safety of calderasib with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There is one primary study hypothesis:

Combination of calderasib and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Inclusion: Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC); Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8; Provides an archival tumor sample (≤5 years) or newly obtained core, incisional, or excisional biopsy or fine needle aspirate (FNA) of a tumor lesion, not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, programmed cell death ligand 1 (PD-L1) status, and biomarker research; If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to < Grade 1 or baseline; If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART); If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load; If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable.

Exclusion: Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease; Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC; Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention; Has received radiotherapy to non-central nervous system (CNS) disease within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis; Has not fully recovered from any effects of major surgical procedure; Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible; Has known history of, or active, neurologic paraneoplastic syndrome; Has an active infection requiring systemic therapy, with exceptions; Has uncontrolled, significant cardiovascular disease or cerebrovascular disease; Known additional malignancy that is progressing or has required active treatment within the past 3 years; Has active autoimmune disease that has required systemic treatment in the past 2 years; Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease; Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease; Has history of allogenic tissue/solid organ transplant; Has known active CNS metastases and/or carcinomatous meningitis.

The main inclusion and exclusion criteria include but are not limited to the following:.

ClinicalTrials.gov NCT06345729 · EU CTIS 2023-507776-42-00