KEYMAKER-U01 Substudy 01J: A Randomized Phase 2 Umbrella Study With Rolling Arms of Investigational Agents for First-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

New lung cancer treatment study for specific mutations

NCT: NCT07252739 · Status: RECRUITING · Phase: Phase 2 · Sponsor: Merck Sharp & Dohme LLC · Started: 2025-12-19 · Est. Completion: 2033-01-14

Plain English Summary

KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J) is a Phase 2 clinical trial sponsored by Merck Sharp & Dohme LLC studying Malignant Neoplasm. This study tests a new drug combination, including pembrolizumab and MK-1084, for advanced or metastatic non-small cell lung cancer (NSCLC) with a specific KRAS G12C gene change. It is for adults with this specific type of lung cancer who have not received prior treatment for their advanced or metastatic disease. Participation involves receiving study medications and regular medical check-ups to monitor for side effects and cancer response. Alternative treatments may include chemotherapy, immunotherapy, or targeted therapies depending on the specific cancer characteristics and prior treatments. The trial aims to enroll 130 participants.

Official Summary

Researchers want to learn if using a study medicine called MK-1084 can help treat NSCLC. MK-1084 is a type of treatment called targeted therapy for the Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C gene change. The goal of this study is to learn about the safety of MK-1084 and to learn how many people have the cancer get smaller or go away during the study treatment.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have been diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. You cannot join if you have small cell lung cancer, certain other medical conditions like active inflammatory bowel disease, or have received prior treatment targeting KRAS. Participants must be able to provide a tumor tissue sample and have recovered from side effects of previous cancer treatments. Specific health conditions like HIV, Hepatitis B, or Hepatitis C must be well-controlled with treatment. This trial is studying Malignant Neoplasm, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the study drugs are, how many patients experience side effects, and how many patients' tumors shrink or disappear, indicating the treatment's effectiveness. The specific primary outcome measures are: Percentage of Participants with a Dose Limiting Toxicity (DLT) (Up to approximately 21 days); Percentage of Participants who Experience at Least One Adverse Event (AE) (Up to approximately 84 months); Percentage of Participants who Discontinue Study Intervention Due to an AE (Up to approximately 84 months); Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR) (Up to approximately 84 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 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatments for a specific subset of lung cancer patients with KRAS G12C mutations, a group for whom targeted therapies are being developed. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Malignant Neoplasm, where improved treatment options are needed.

Investor Insight

This trial is investigating a novel targeted therapy combination for a genetically defined lung cancer population, representing a significant market opportunity if successful, with Merck as the sponso Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of participating in this study and how it compares to standard treatments. Understand that participation involves regular visits for drug administration, blood tests, scans, and monitoring for side effects. Be prepared for potential side effects, which will be closely monitored by the study team. This trial is currently recruiting participants. The trial is being conducted at 15 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

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has histologically or cytologically confirmed diagnosis of advanced or metastatic nonsquamous Non-Small Cell Lung Cancer (NSCLC)
* Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations
* Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated
* Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement
* Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected
* Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive
* Has undetectable hepatitis C (HCV) viral load if HCV-infected

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Has HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
* Has uncontrolled, clinically significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval corrected for heart rate by Fridericia's formula (QTcF) interval to \>470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
* Has received prior systemic anticancer therapy for advanced or metastatic NSCLC
* Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
* Has received previous treatment with an agent targeting KRAS
* Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from AE associated with anticancer therapy before allocation/randomization
* Has received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications

Trial Locations

Frequently Asked Questions

What is clinical trial NCT07252739?

NCT07252739 is a Phase 2 INTERVENTIONAL study titled "KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J)." It is currently recruiting and is sponsored by Merck Sharp & Dohme LLC. The trial targets enrollment of 130 participants.

What conditions does NCT07252739 study?

This trial investigates treatments for Malignant Neoplasm. The primary condition under study is Malignant Neoplasm.

What treatments are being tested in NCT07252739?

The interventions being studied include: MK-1084 (DRUG), Pembrolizumab (BIOLOGICAL), Cetuximab (BIOLOGICAL), Carboplatin (DRUG), Pemetrexed (DRUG). Oral Administration

What does Phase 2 mean for NCT07252739?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT07252739?

This trial is currently "Recruiting." It started on 2025-12-19. The estimated completion date is 2033-01-14.

Who is sponsoring NCT07252739?

NCT07252739 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 NCT07252739?

The trial aims to enroll 130 participants. The trial is currently recruiting and accepting new participants.

How is NCT07252739 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs single 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 NCT07252739?

The primary outcome measures are: Percentage of Participants with a Dose Limiting Toxicity (DLT) (Up to approximately 21 days); Percentage of Participants who Experience at Least One Adverse Event (AE) (Up to approximately 84 months); Percentage of Participants who Discontinue Study Intervention Due to an AE (Up to approximately 84 months); Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR) (Up to approximately 84 months). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT07252739 being conducted?

This trial is being conducted at 15 sites, including Clermont, Florida; Helsinki, Uusimaa; Deventer, Overijssel; Leiden, South Holland and 11 more sites (United States, Finland, Netherlands).

Where can I find official information about NCT07252739?

The official record for NCT07252739 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT07252739. This government database provides the most up-to-date and detailed information about the trial.

What is NCT07252739 testing in simple terms?

This study tests a new drug combination, including pembrolizumab and MK-1084, for advanced or metastatic non-small cell lung cancer (NSCLC) with a specific KRAS G12C gene change. It is for adults with this specific type of lung cancer who have not received prior treatment for their advanced or metastatic disease.

Why is this trial significant?

This trial addresses a need for new treatments for a specific subset of lung cancer patients with KRAS G12C mutations, a group for whom targeted therapies are being developed.

What are the potential risks of participating in NCT07252739?

Common side effects may include fatigue, nausea, rash, and changes in blood counts. More serious risks can include immune system reactions affecting organs like the lungs, liver, or skin, and potential heart-related issues. Specific side effects related to MK-1084 and pembrolizumab will be closely monitored and managed by the study team. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT07252739?

Ask your doctor about the specific risks and benefits of participating in this study and how it compares to standard treatments. Understand that participation involves regular visits for drug administration, blood tests, scans, and monitoring for side effects. Be prepared for potential side effects, which will be closely monitored by the study team. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT07252739 signal from an investment perspective?

This trial is investigating a novel targeted therapy combination for a genetically defined lung cancer population, representing a significant market opportunity if successful, with Merck as the sponso This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participation involves receiving study medications and regular medical check-ups to monitor for side effects and cancer response. 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.