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A Study of Calderasib (MK-1084) Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)

RecruitingPhase 3

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)

Who can join

Ages 18 and older · All sexes

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

Inclusion Criteria:

* 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 tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, 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 Criteria:

* Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
* 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
* Has one or more of the following ophthalmological findings/conditions: intraocular pressure \>21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative 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 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 known active central nervous system metastases and/or carcinomatous meningitis
* 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 not fully recovered from any effects of major surgical procedure

About the study

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 are two primary study hypotheses:

Hypothesis 1: 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).

Hypothesis 2: Combination of calderasib plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).

What is being tested

Sponsor: Merck Sharp & Dohme LLC · Participants: 600 · Started: May 24, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06345729

Locations in the U.S.

CaliforniaCBCC Global Research, Inc. ( Site 0123), Bakersfield
Beverly Hills Cancer Center ( Site 0116), Beverly Hills
ConnecticutStamford Hospital ( Site 0136), Stamford
IllinoisOrchard Healthcare Research Inc. ( Site 0115), Skokie
MissouriTruman Medical Center ( Site 0126), Kansas City
Cox Medical Center North ( Site 0133), Springfield
MontanaSt. Vincent Frontier Cancer Center-Research ( Site 0105), Billings
New JerseyAtlantic Health System Morristown Medical Center ( Site 0121), Morristown
New YorkNew York Oncology Hematology, P.C. ( Site 0132), Albany
OhioUniversity of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0103), Cincinnati
PennsylvaniaLancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0134), Lancaster
TexasOncology Consultants P.A. ( Site 0113), Houston
WisconsinCircuit Clinical/SSM Health Dean Medical Group ( Site 0129), Madison

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.