UPCC 32524 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)

Investigating the Effectiveness of an Investigational Medication Combined with Pembrolizumab Immunotherapy in Advanced Lung Cancer with KRAS G12C Mutation

Enrolling By Invitation
18 years or above
All
Phase 3
600 participants needed
1 Location

Brief description of 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).

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-small Cell Lung Cancer
  • Age: 18 years or above
  • Gender: All

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

This study investigates the effectiveness and safety of an investigational medication combined with pembrolizumab as a first-line treatment for individuals with locally advanced or metastatic non-small cell lung cancer (NSCLC). The cancer must have a specific mutation called KRAS G12C and a PD-L1 tumor proportion score of 50% or higher. The purpose is to compare this combination treatment to a placebo with pembrolizumab, focusing on progression-free survival and overall survival rates.

Participants in the study will be randomly assigned to one of two study arms. One group will receive the investigational medication along with pembrolizumab, while the other group will receive a placebo with pembrolizumab. The study will use Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) to assess the treatment's impact on the cancer. Participants will undergo regular health checks and monitoring to ensure their safety and the effectiveness of the treatment.

  • Who can participate: Adults with a confirmed diagnosis of non-small cell lung cancer (NSCLC) that is either Stage IIIB/IIIC or Stage IV may participate. They must have a KRAS G12C mutation and a PD-L1 TPS of 50% or more. Participants should not have had previous systemic treatment for their advanced NSCLC.
  • Study details: Participants will be assigned to receive either the investigational medication with pembrolizumab or a placebo with pembrolizumab. The investigational medication is being tested for its potential benefits in cancer treatment. Participants will be monitored for any side effects and treatment response.
Updated on 06 Oct 2026. Study ID: 25-0094
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