RecruitingPHASE3INTERVENTIONAL

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)

This research study is for people with advanced non-small cell lung cancer (a common type of lung cancer) that hasn't been treated yet. Specifically, it's for those whose cancer has a particular gene change called KRAS G12C. The study is comparing two different treatment approaches: one group will receive a new drug called adagrasib alongside pembrolizumab and standard chemotherapy, while the other group will receive a placebo (an inactive substance) with pembrolizumab and chemotherapy. The main goal is to see if adding adagrasib makes the treatment more effective, if it's safe, and how well people tolerate it. This is a Phase 3 study, meaning it's in the later stages of testing new treatments.

At a glance

Status

Recruiting

Phase

PHASE3

Sponsor

Mirati Therapeutics Inc.

Enrolment target

630

Start

24 Apr 2025

Estimated completion

30 Apr 2032

Carcinoma, Non-Small-Cell Lung

What is this study about?

This clinical trial, called KRYSTAL-4, is investigating a new treatment approach for a specific type of lung cancer. It's for people who have non-small cell lung cancer (NSCLC), which is the most common kind of lung cancer, and whose cancer has advanced or spread. A key detail is that their cancer must have a particular genetic alteration known as a KRAS G12C mutation. This mutation means the cancer cells have a faulty protein that helps them grow.

The study involves comparing two different treatment combinations. Everyone in the study will receive standard chemotherapy (either carboplatin and pemetrexed or cisplatin and pemetrexed) along with a drug called pembrolizumab, which is a type of immunotherapy. Half of the participants will also receive a new drug called adagrasib, specifically designed to target the KRAS G12C mutation. The other half will receive a placebo, which looks like adagrasib but contains no active medicine. This comparison helps researchers understand if adding adagrasib makes the treatment more effective and safer.

The main aim of this study is to see how well these drug combinations work for people who haven't had previous treatment for their advanced lung cancer. Researchers will carefully check how much the treatment shrinks the cancer, how long people live without their cancer getting worse, and also look at any side effects people might experience. This is a Phase 3 study, which means it’s one of the final steps before a new drug might be approved for wider use.

Key takeaways

This study is for people with advanced, previously untreated non-small cell lung cancer that has a specific KRAS G12C gene change.
It compares adding a new drug (adagrasib) to standard chemotherapy and pembrolizumab, against chemotherapy and pembrolizumab with a placebo.
The aim is to see if adagrasib improves treatment effectiveness and safety.
Participation involves regular hospital visits, monitoring, and detailed health checks.
You'll be closely monitored for side effects, and you can withdraw from the study at any time.

Who may be eligible?

To be considered for this study, you would need to have been diagnosed with advanced non-small cell lung cancer that hasn't been treated before. A very important factor is that your cancer must have a specific genetic change called a KRAS G12C mutation, which doctors can check from a sample of your tumour or blood. Your cancer also needs to be visible on scans like CT or MRI.

There are also some reasons why you might not be able to join. For example, if you have certain existing medical conditions like active autoimmune diseases needing treatment, or significant heart problems that are not well controlled, you might not be eligible. Also, you can't have been previously treated for your advanced lung cancer, nor can you have received other drugs specifically designed to target the KRAS G12C mutation like sotorasib or adagrasib.

Even if you have brain metastases (cancer that has spread to the brain), you might still be able to join, as long as they aren't causing symptoms and don't need immediate treatment, and are not too large. The study is open to both men and women aged 18 and over.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Have I been diagnosed with advanced non-small cell lung cancer that has not been treated before for its advanced stage?
Does my cancer have a KRAS G12C gene change, confirmed by a test?
Do I have visible cancer on scans (like CT or MRI)?
Have I previously taken any drugs specifically targeting the KRAS G12C mutation?
Do I have any serious, uncontrolled health conditions like severe heart disease or active autoimmune disease?
Am I at least 18 years old?

Answer every question to see your result.

What does participation involve?

If you decide to take part in this study, you will be allocated by chance to one of two treatment groups – either the group receiving adagrasib, pembrolizumab, and chemotherapy, or the group receiving a placebo, pembrolizumab, and chemotherapy. You won't be able to choose which group you are in, and neither will your doctor. You will receive your treatment, typically through intravenous infusions (into a vein) and possibly oral tablets, over several cycles.

You will have regular hospital visits for check-ups, blood tests, and scans (like CT or MRI) to monitor your health and how well the treatment is working. The exact schedule will be detailed by the study team, but these visits are crucial for safety and monitoring the cancer. You will also be asked about any side effects you experience. The duration of your participation will depend on how you respond to the treatment and until your doctor decides that continuing the study treatment is no longer in your best interest, or if significant side effects occur. After stopping treatment, there will be a follow-up period to continue monitoring your health.

Potential risks and benefits

Participating in a clinical trial offers some potential benefits, such as receiving state-of-the-art medical care and access to a new drug (adagrasib) that might be more effective for your specific type of lung cancer than standard treatment alone. However, joining a study also comes with potential risks, including side effects from the experimental drugs and standard treatments, which can vary from mild to severe. As with any medical treatment, there's also no guarantee that the treatment will be effective for you. You will be closely monitored by a medical team for any side effects or changes in your health. Remember, deciding whether or not to participate is entirely your choice, and you are free to withdraw from the study at any time without it affecting your future medical care.

Locations (353)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Local Institution - 0347
Verified postcode
Birmingham, United States· Not yet recruiting
Local Institution - 0686
Verified postcode
Springdale, United States· Not yet recruiting
Local Institution - 0581
Verified postcode
Fullerton, United States· Not yet recruiting
Local Institution - 0682
Verified postcode
Loma Linda, United States· Not yet recruiting
Helios Clinical Research
Verified postcode
Long Beach, United States· Recruiting
Local Institution - 0442
Verified postcode
Denver, United States· Not yet recruiting
Local Institution - 0701
Verified postcode
Newark, United States· Not yet recruiting
Local Institution - 0694
Verified postcode
Clearwater, United States· Not yet recruiting
Cancer Specialists of North Florida
Verified postcode
Jacksonville, United States· Recruiting
Local Institution - 0696
Verified postcode
Miami, United States· Not yet recruiting
Local Institution - 0680
Verified postcode
Ocala, United States· Not yet recruiting
Mid Florida Hematology and Oncology Center
Verified postcode
Orange City, United States· Recruiting

Common questions

What is a KRAS G12C mutation?

It's a specific change in the KRAS gene within your cancer cells that can cause them to grow uncontrollably. This study is for people whose cancer has this particular change.

What does 'non-small cell lung cancer' mean?

This is the most common type of lung cancer. The study focuses on advanced disease that has not been treated before.

What is a 'placebo'?

A placebo looks just like the study drug but doesn't contain any active medicine. It helps researchers compare the effects of the new drug.

Will I know if I'm getting the new drug or the placebo?

No, this is a 'blinded' study, meaning neither you nor your doctors will know which treatment you are receiving until the study is over, unless there's a medical need to find out.

How long will the study last?

The length of time you participate will depend on how your body responds to the treatment and your health and safety. The study team will provide more specific details.

How to find out more

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

clinical.trials@bms.com 855-907-3286 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.