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RecruitingLast updated: 14 May 2026

KANDLELIT-004: A medicine called calderasib when given with immunotherapy as first-line treatment in people with advanced non-small cell lung cancer with KRAS G12C mutation and PD-L1 TPS ≥50%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, Metastatic NSCLC With PD-L1 TPS ≥50%

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

KANDLELIT-004

Clinical summary

Summary

This study is testing a new treatment combination for people with advanced lung cancer (non-small cell lung cancer) that has spread or cannot be treated with surgery. The cancer must have a specific gene change called KRAS G12C and a high level of a protein called PD-L1. Participants must also not have received any systemic therapy for their locally advanced or metastatic disease, but treatment for an earlier stage may be permitted.

Participants will receive:

  • pembrolizumab (an immunotherapy), plus
  • either calderasib (a new targeted drug, also known as MK-1084) or a placebo.

People are randomly assigned (by chance) to receive one of these treatment options, and neither they nor the study team will know who is receiving calderasib or placebo.

What the study is trying to find out
Researchers want to see if adding calderasib to pembrolizumab can:

  • Help people live longer without their cancer getting worse, and
  • Help people live longer overall.

The study is based on the idea that the new combination may work better than pembrolizumab alone, but this needs to be tested.

 

Conditions

This trial is treating people with newly diagnosed metastatic non-small cell lung cancer with KRAS G12C mutation and PD-L1 expression of ≥50%

Eligibility

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 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

  • 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • You are able to swallow medication by mouth.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:

  • NCT06345729 *
  • 2023-507776-42-00 *
  • MK-1084-004; U1111-1296-8093; JRCT2031240213; PHRR241128-007796;

Trial sponsor

Merck Sharp & Dohme LLC

Scientific Title

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, Metastatic NSCLC With PD-L1 TPS ≥50%

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