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)
New Lung Cancer Treatment Study for Specific Genetic Mutation
Plain English Summary
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) is a Phase 3 clinical trial sponsored by Merck Sharp & Dohme LLC studying Non-small Cell Lung Cancer. This study tests a new drug combination (calderasib and pembrolizumab) against a standard treatment (pembrolizumab alone) for advanced lung cancer. It is for patients with non-small cell lung cancer (NSCLC) that has a specific genetic change (KRAS G12C mutation) and high levels of PD-L1. Participation involves receiving either the new combination therapy or the standard therapy, with regular check-ups and tests. Alternatives include other standard chemotherapy, immunotherapy, or targeted therapies depending on the specific cancer characteristics and prior treatments. The trial aims to enroll 600 participants.
Official Summary
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).
Who Can Participate
Here is what you need to know about eligibility for this trial. Patients with newly diagnosed non-small cell lung cancer (NSCLC) that has spread or cannot be surgically removed. Must have a confirmed KRAS G12C mutation and PD-L1 levels of 50% or higher in their tumor. Patients must be at least 18 years old and have recovered from any recent side effects of prior cancer treatments. Cannot have active brain metastases, certain autoimmune conditions, or active infections requiring treatment. This trial is studying Non-small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.
What They're Measuring
The study will measure how long patients live without their cancer getting worse (progression-free survival) and their overall survival, meaning how long they live in total. The specific primary outcome measures are: Progression-Free Survival (PFS) (Up to approximately 42 months); Overall Survival (OS) (Up to approximately 56 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.
About This Phase
This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.
Why This Trial Matters
This trial addresses a critical need for more effective first-line treatments for a specific subset of lung cancer patients with a common genetic mutation. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Non-small Cell Lung Cancer, where improved treatment options are needed.
Investor Insight
This trial targets a growing market for lung cancer therapies, particularly those with specific genetic markers, and aims to improve upon existing immunotherapy standards. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 600 participants suggests significant investment in this program.
Is This Trial Right for Me?
Ask your doctor if your lung cancer has the KRAS G12C mutation and if your PD-L1 levels are high enough for this study. Participation involves regular clinic visits for treatment, scans to monitor your cancer, and blood tests. You will receive either the new drug combination or the standard treatment, and your health will be closely monitored for side effects. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.
AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.
Study Design
- Study Type: INTERVENTIONAL
- Allocation: RANDOMIZED
- Model: PARALLEL
- Masking: TRIPLE
- Enrollment: 600 participants
Interventions
- DRUG: Calderasib — Oral tablets
- OTHER: Placebo — Oral tablets
- BIOLOGICAL: Pembrolizumab — IV infusion
Primary Outcomes
- Progression-Free Survival (PFS) (Up to approximately 42 months)
- Overall Survival (OS) (Up to approximately 56 months)
Secondary Outcomes
- Objective Response Rate (ORR) (Up to approximately 42 months)
- Duration of Response (DOR) (Up to approximately 42 months)
- Number of Participants Who Experience One or More Adverse Event (AEs) (Up to approximately 56 months)
- Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) (Up to approximately 56 months)
- Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score (Baseline and Up to approximately 24 months)
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
Trial Locations
- 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
- ...and 10 more locations
Frequently Asked Questions
What is clinical trial NCT06345729?
NCT06345729 is a Phase 3 INTERVENTIONAL study titled "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)." It is currently recruiting and is sponsored by Merck Sharp & Dohme LLC. The trial targets enrollment of 600 participants.
What conditions does NCT06345729 study?
This trial investigates treatments for Non-small Cell Lung Cancer. The primary condition under study is Non-small Cell Lung Cancer.
What treatments are being tested in NCT06345729?
The interventions being studied include: Calderasib (DRUG), Placebo (OTHER), Pembrolizumab (BIOLOGICAL). Oral tablets
What does Phase 3 mean for NCT06345729?
Phase 3 trials are large-scale studies involving 300-3,000+ patients that compare the new treatment against existing standard treatments. Positive Phase 3 results are typically required for FDA approval.
What is the current status of NCT06345729?
This trial is currently "Recruiting." It started on 2024-05-24. The estimated completion date is 2031-02-18.
Who is sponsoring NCT06345729?
NCT06345729 is sponsored by Merck Sharp & Dohme LLC. The sponsor is responsible for funding, designing, and overseeing the clinical trial.
How many people can participate in NCT06345729?
The trial aims to enroll 600 participants. The trial is currently recruiting and accepting new participants.
How is NCT06345729 designed?
This is a interventional study, uses randomized allocation, follows a parallel design, employs triple masking. Masking means some participants and/or investigators do not know which treatment group a participant is in, which helps reduce bias.
What are the primary outcomes being measured in NCT06345729?
The primary outcome measures are: Progression-Free Survival (PFS) (Up to approximately 42 months); Overall Survival (OS) (Up to approximately 56 months). These are the main endpoints researchers use to determine whether the treatment is effective.
Where is NCT06345729 being conducted?
This trial is being conducted at 20 sites, including Bakersfield, California; Beverly Hills, California; Stamford, Connecticut; Miami Beach, Florida and 16 more sites (United States, Argentina).
Where can I find official information about NCT06345729?
The official record for NCT06345729 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06345729. This government database provides the most up-to-date and detailed information about the trial.
What is NCT06345729 testing in simple terms?
This study tests a new drug combination (calderasib and pembrolizumab) against a standard treatment (pembrolizumab alone) for advanced lung cancer. It is for patients with non-small cell lung cancer (NSCLC) that has a specific genetic change (KRAS G12C mutation) and high levels of PD-L1.
Why is this trial significant?
This trial addresses a critical need for more effective first-line treatments for a specific subset of lung cancer patients with a common genetic mutation. As a Phase 3 trial, positive results could lead directly to regulatory approval and new treatment options for patients.
What are the potential risks of participating in NCT06345729?
Common side effects may include fatigue, nausea, diarrhea, and skin rash. More serious risks can include lung inflammation, liver problems, or heart issues. Your doctor will monitor you closely for any side effects and manage them as needed. As with any clinical trial, participants are closely monitored and can withdraw at any time.
Should I consider participating in NCT06345729?
Ask your doctor if your lung cancer has the KRAS G12C mutation and if your PD-L1 levels are high enough for this study. Participation involves regular clinic visits for treatment, scans to monitor your cancer, and blood tests. You will receive either the new drug combination or the standard treatment, and your health will be closely monitored for side effects. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.
What does NCT06345729 signal from an investment perspective?
This trial targets a growing market for lung cancer therapies, particularly those with specific genetic markers, and aims to improve upon existing immunotherapy standards. This is a Phase 3 trial, which is the final pivotal stage before potential regulatory submission.
What happens if the treatment in this trial doesn't work?
Participation involves receiving either the new combination therapy or the standard therapy, with regular check-ups and tests. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.
Related Conditions
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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.