A Randomized, Double-Blind, Phase 3 Trial of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

New Lung Cancer Trial Tests Targeted Therapy with Chemo and Immunotherapy

NCT: NCT06875310 · Status: RECRUITING · Phase: Phase 3 · Sponsor: Mirati Therapeutics Inc. · Started: 2025-04-24 · Est. Completion: 2032-04-30

Plain English Summary

A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4) is a Phase 3 clinical trial sponsored by Mirati Therapeutics Inc. studying Carcinoma, Non-Small-Cell Lung. This trial tests a combination of adagrasib (a targeted drug), pembrolizumab (an immunotherapy), and chemotherapy against a placebo with pembrolizumab and chemotherapy. It is for adults with non-small cell lung cancer that has spread or cannot be fully removed, and has a specific KRAS G12C mutation, who have not received prior treatment for advanced disease. Participation involves receiving one of the study treatments, regular medical check-ups, and tests to monitor the cancer and overall health. Alternative treatments may include other chemotherapy regimens, immunotherapy, or targeted therapies depending on the specific cancer characteristics and prior treatments. The trial aims to enroll 630 participants.

Official Summary

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with a confirmed diagnosis of non-squamous non-small cell lung cancer and a KRAS G12C mutation. Individuals with cancer that has spread to other parts of the body or cannot be fully removed by surgery or radiation. Patients who have not received any prior systemic treatment for their advanced or metastatic lung cancer. People with brain metastases are eligible if they are asymptomatic and do not require immediate treatment, and are no larger than 20 mm. This trial is studying Carcinoma, Non-Small-Cell Lung, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes, Progression Free Survival and Overall Survival, measure how long patients live without their cancer getting worse and their total lifespan, respectively, indicating how effective The specific primary outcome measures are: Progression Free Survival (PFS) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR) (Up to 7 years); Overall Survival (OS) (Up to 7 years). 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 aims to fill a treatment gap for lung cancer patients with a specific KRAS G12C mutation by investigating a novel combination therapy that targets the cancer's growth mechanism while also b 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 Carcinoma, Non-Small-Cell Lung, where improved treatment options are needed.

Investor Insight

This trial targets a specific genetic mutation (KRAS G12C) in a large cancer market, with potential for significant improvement over existing therapies, suggesting a strong investment signal if succes Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 630 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific type of lung cancer and if you have the KRAS G12C mutation. Understand that you will be randomly assigned to receive either the study drug combination or a placebo with standard treatment. Be prepared for regular visits for treatment, blood tests, scans to check your cancer, and monitoring 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

Interventions

Primary Outcomes

Secondary Outcomes

Full Eligibility Criteria

Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA).
* Locally advanced or metastatic disease.
* Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
* No prior systemic anti-cancer therapy given for advanced or metastatic disease.
* Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection).
* Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
* Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.

Exclusion Criteria:

* Participants with an active autoimmune or inflammatory disease requiring systemic treatment within 2 years.
* Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment that are ongoing or with risk of recurrence.
* Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.
* Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry.
* Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Trial Locations

Frequently Asked Questions

What is clinical trial NCT06875310?

NCT06875310 is a Phase 3 INTERVENTIONAL study titled "A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)." It is currently recruiting and is sponsored by Mirati Therapeutics Inc.. The trial targets enrollment of 630 participants.

What conditions does NCT06875310 study?

This trial investigates treatments for Carcinoma, Non-Small-Cell Lung. The primary condition under study is Carcinoma, Non-Small-Cell Lung.

What treatments are being tested in NCT06875310?

The interventions being studied include: Adagrasib (DRUG), Pembrolizumab (DRUG), Carboplatin (DRUG), Pemetrexed (DRUG), Placebo (DRUG). Specified dose on specified days

What does Phase 3 mean for NCT06875310?

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 NCT06875310?

This trial is currently "Recruiting." It started on 2025-04-24. The estimated completion date is 2032-04-30.

Who is sponsoring NCT06875310?

NCT06875310 is sponsored by Mirati Therapeutics Inc.. The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06875310?

The trial aims to enroll 630 participants. The trial is currently recruiting and accepting new participants.

How is NCT06875310 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs quadruple 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 NCT06875310?

The primary outcome measures are: Progression Free Survival (PFS) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR) (Up to 7 years); Overall Survival (OS) (Up to 7 years). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06875310 being conducted?

This trial is being conducted at 20 sites, including Birmingham, Alabama; Springdale, Arkansas; Fullerton, California; Loma Linda, California and 16 more sites (United States).

Where can I find official information about NCT06875310?

The official record for NCT06875310 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06875310. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06875310 testing in simple terms?

This trial tests a combination of adagrasib (a targeted drug), pembrolizumab (an immunotherapy), and chemotherapy against a placebo with pembrolizumab and chemotherapy. It is for adults with non-small cell lung cancer that has spread or cannot be fully removed, and has a specific KRAS G12C mutation, who have not received prior treatment for advanced disease.

Why is this trial significant?

This trial aims to fill a treatment gap for lung cancer patients with a specific KRAS G12C mutation by investigating a novel combination therapy that targets the cancer's growth mechanism while also b 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 NCT06875310?

Common side effects may include fatigue, nausea, diarrhea, and skin rash. More serious risks can include lung inflammation, liver problems, heart issues, and severe allergic reactions. The combination of drugs may also lead to side effects related to chemotherapy and immunotherapy, such as low blood cell counts or immune system overactivity. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06875310?

Ask your doctor if this trial is a good fit for your specific type of lung cancer and if you have the KRAS G12C mutation. Understand that you will be randomly assigned to receive either the study drug combination or a placebo with standard treatment. Be prepared for regular visits for treatment, blood tests, scans to check your cancer, and monitoring for side effects. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06875310 signal from an investment perspective?

This trial targets a specific genetic mutation (KRAS G12C) in a large cancer market, with potential for significant improvement over existing therapies, suggesting a strong investment signal if succes 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 one of the study treatments, regular medical check-ups, and tests to monitor the cancer and overall health. 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.

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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.