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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

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)

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)

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) (NCT06345729) is a Phase 3 interventional studying Non-small Cell Lung Cancer, sponsored by Merck Sharp & Dohme LLC. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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 Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Non-small Cell Lung Cancer, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 600 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

The main inclusion and exclusion criteria include but are not limited to the following: Who May Qualify: - Has diagnosed by tissue sample (biopsy-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 weakened immune system 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 Who Should NOT Join This Trial: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

DRUG

Calderasib

Oral tablets

OTHER

Placebo

Oral tablets

BIOLOGICAL

Pembrolizumab

IV infusion

Locations (20)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

CBCC Global Research, Inc. ( Site 0123)
Bakersfield, California, United States
Beverly Hills Cancer Center ( Site 0116)
Beverly Hills, California, United States
Stamford Hospital ( Site 0136)
Stamford, Connecticut, United States
Mount Sinai Cancer Center ( Site 0137)
Miami Beach, Florida, United States
Orchard Healthcare Research Inc. ( Site 0115)
Skokie, Illinois, United States
Truman Medical Center ( Site 0126)
Kansas City, Missouri, United States
Cox Medical Center North ( Site 0133)
Springfield, Missouri, United States
St. Vincent Frontier Cancer Center-Research ( Site 0105)
Billings, Montana, United States
Atlantic Health System Morristown Medical Center ( Site 0121)
Morristown, New Jersey, United States
New York Oncology Hematology, P.C. ( Site 0132)
Albany, New York, United States
University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0103)
Cincinnati, Ohio, United States
Kettering Health Main Campus-Kettering Health Cancer Center ( Site 0106)
Kettering, Ohio, United States
Lancaster General Hospital - Ann B Barshinger Cancer Institute ( Site 0134)
Lancaster, Pennsylvania, United States
Oncology Consultants P.A. ( Site 0113)
Houston, Texas, United States
Circuit Clinical/SSM Health Dean Medical Group ( Site 0129)
Madison, Wisconsin, United States
AUSTRAL MEDICAL CENTER ( Site 0302)
CABA, Buenos Aires, Argentina
Centro Oncologico Korben ( Site 0304)
CABA, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Mar del Plata ( Site 0300)
Mar del Plata, Buenos Aires, Argentina
Fundacion Estudios Clinicos ( Site 0306)
Rosario, Santa Fe Province, Argentina
Sanatorio Parque ( Site 0301)
Rosario, Santa Fe Province, Argentina

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06345729), the sponsor (Merck Sharp & Dohme LLC), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06345729 clinical trial studying?

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 Vers… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06345729?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06345729?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06345729. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06345729. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.