Adagrasib for KRAS-Mutated Lung Cancer

Recruiting at 283 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mirati Therapeutics Inc.

Must not be taking: Steroids, KRAS inhibitors

Disqualifiers: Brain lesions, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called adagrasib (also known as Krazati or MRTX-849) for individuals with a specific type of lung cancer that has a KRAS G12C mutation. Researchers aim to evaluate the effectiveness of two different doses for treating this cancer. The trial seeks participants whose cancer has spread and who have already undergone chemotherapy and immune checkpoint inhibitors. It is not suitable for those who have previously received a KRAS G12C targeted treatment or have certain untreated brain conditions. Participants must have recovered from their previous cancer treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you have certain medical conditions or need to take certain medications that could make it unsafe, a trial doctor might advise changes.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that adagrasib is generally safe for people with KRAS-mutated non-small-cell lung cancer (NSCLC). In earlier studies, patients who took adagrasib did not experience unexpected or dangerous side effects.

Studies have found that adagrasib is well-tolerated, with most side effects being mild and manageable. This is important because it allows most people to continue treatment without serious problems.

Adagrasib has been used in patients before and demonstrated benefits without causing new safety issues. This supports the idea that the treatment is safe for people with this specific type of lung cancer.

Overall, current evidence suggests that adagrasib is a safe option for those considering joining a clinical trial for KRAS-mutated lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Adagrasib for KRAS-mutated lung cancer because it targets a specific mutation in the KRAS gene, which is a common driver of cancer cell growth. Unlike standard treatments like chemotherapy, which attack rapidly dividing cells in general, Adagrasib specifically inhibits the KRAS G12C mutation, potentially leading to more effective and targeted therapy with fewer side effects. Additionally, Adagrasib is available in two formulations: one taken without regard to food at 600mg twice daily, and another taken with food at 400mg twice daily, offering flexibility in dosing that can improve patient convenience and adherence.

What evidence suggests that adagrasib might be an effective treatment for KRAS-mutated lung cancer?

In previous studies, adagrasib has shown promising results for treating KRAS G12C-mutated non-small cell lung cancer (NSCLC). Research indicates that patients taking adagrasib experienced longer periods without cancer progression, known as improved progression-free survival. One study showed that adagrasib delayed cancer progression more effectively than the usual treatment, docetaxel. This trial will test different dosages of adagrasib, specifically 600mg BID and 400mg BID. Additionally, another study found that combining adagrasib with pembrolizumab, a drug that boosts the immune system, further improved survival rates. These findings suggest that adagrasib could be a strong option for people with this specific type of lung cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic NSCLC who have the KRAS G12C mutation and previously underwent chemotherapy including cisplatin or carboplatin, plus immune checkpoint inhibitors. They should be recovered from prior treatments with safe blood test levels. Those ineligible include patients who could undergo surgery to remove cancer, those treated before with KRAS G12C targeting drugs, individuals with certain medical conditions or on conflicting medications, pregnant women, and patients with specific brain lesions.

Inclusion Criteria

I am at least 18 years old or legally considered an adult.

Have recovered from their prior treatment and blood tests are within a safe range

I've been treated with chemotherapy involving cisplatin or carboplatin and an immune therapy.

Exclusion Criteria

My cancer is considered operable.

I have been treated with a drug for KRAS G12C mutation.

Have certain medical conditions or need to take certain medications that, in the opinion of a trial doctor, could make it unsafe for them to participate or difficult to complete the trial assessments, or are pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adagrasib monotherapy with two dosing regimens (600 mg BID without regard to food versus 400 mg BID with food)

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including patient-reported outcomes and quality of life assessments

30 months

Long-term Follow-up

Evaluate overall survival and progression-free survival

45 months

What Are the Treatments Tested in This Trial?

Interventions

• Adagrasib

Trial Overview

The KRYSTAL 21 study is testing two different doses of a drug called Adagrasib (600 mg twice daily vs. 400 mg twice daily) in patients who have non-small cell lung cancer (NSCLC) that carries a specific genetic change known as the KRAS G12C mutation.

How Is the Trial Designed?

Group I: Adagrasib 600mg BID Experimental Treatment 1 Intervention

Adagrasib 600mg BID without regard to food

Group II: Adagrasib 400mg BID Experimental Treatment 1 Intervention

Adagrasib 400mg BID with food

Adagrasib is already approved in United States, European Union for the following indications:

Approved in United States as Krazati for:

• KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
• KRAS G12C-mutated locally advanced or metastatic colorectal cancer

Approved in European Union as Krazati for:

• KRAS G12C mutation non-small cell lung cancer

Who Is Running the Clinical Trial?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

Adagrasib, a newly approved KRASG12C-targeted therapy, shows a clinical efficacy with an objective response rate of 42.9% and a median duration of response of 8.5 months in patients with advanced KRASG12C-mutated non-small-cell lung cancer.

While adagrasib is effective, it is associated with a high incidence of treatment-related adverse events, primarily gastrointestinal, affecting 97.4% of patients, with 44.8% experiencing severe (grade 3+) side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib: a novel inhibitor for KRASG12C-mutated non-small-cell lung cancer. Guo, MZ., Marrone, KA., Spira, A., et al.[2023]

In a phase I/IB study involving 25 patients with advanced KRASG12C-mutant solid tumors, adagrasib (600 mg twice daily) demonstrated significant antitumor activity, with 53.3% of patients with non-small-cell lung cancer achieving a confirmed partial response after a median follow-up of 19.6 months.

Adagrasib was well tolerated, with the most common side effects being nausea (80%), diarrhea (70%), and fatigue (45%), indicating a manageable safety profile for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). Ou, SI., Jänne, PA., Leal, TA., et al.[2023]

Adagrasib (KRAZATI™) is an effective oral treatment specifically targeting the KRAS G12C mutation in solid tumors, particularly non-small cell lung cancer (NSCLC), by locking the mutant protein in an inactive state, which prevents cancer cell signaling.

In December 2022, adagrasib received accelerated approval in the USA for adults with KRAS G12C-mutated NSCLC who have undergone prior systemic therapy, based on its promising response rates, although further confirmatory trials are needed to establish its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib: First Approval. Dhillon, S.[2023]

The KRYSTAL-1 study found that adagrasib (MRTX849), a KRASG12c inhibitor, is generally well tolerated by patients with non-small cell lung cancer, indicating a favorable safety profile.

Adagrasib demonstrated significant efficacy in treating non-small cell lung cancer with the KRASG12c mutation, and it also showed some activity in colorectal cancer and other solid tumors, although to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

Adagrasib (MRTX849) is a selective inhibitor targeting the KRASG12C mutation, which is common in non-small cell lung cancer (NSCLC) and linked to poor patient outcomes.

Recent Phase I/II studies have demonstrated that adagrasib shows promising efficacy and tolerability, marking a significant advancement in the treatment of KRASG12C-driven NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib. Brazel, D., Arter, Z., Nagasaka, M.[2022]

Adagrasib (MRTX849) is a promising treatment for patients with KRAS-mutant non-small cell lung cancer (NSCLC) and brain metastases, showing the ability to penetrate the central nervous system and achieve effective concentrations in cerebrospinal fluid.

In preclinical models and preliminary clinical data from two patients, adagrasib demonstrated tumor regression in brain metastases, indicating its potential efficacy in treating this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Sabari, JK., Velcheti, V., Shimizu, K., et al.[2023]

Citations

1.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2204619

Adagrasib in Non–Small-Cell Lung Cancer Harboring a ...

In patients with previously treated KRASG12C-mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11534526/

Adagrasib in KRYSTAL-12 has Broken the KRASG12C ...

The Phase III KRYSTAL-12 trial demonstrated that adagrasib significantly improved median progression-free survival (mPFS) compared with ...

3.

news.bms.com

news.bms.com/news/details/2024/KRAZATI-adagrasib-Demonstrated-Statistically-Significant-Improvement-in-Progression-Free-Survival-in-Patients-with-Pretreated-Locally-Advanced-or-Metastatic-KRASG12C-Mutated-Non-Small-Cell-Lung-Cancer/default.aspx

KRAZATI (adagrasib) Demonstrated Statistically Significant ...

First presentation of data from Phase 3 KRYSTAL-12 study showed statistically significant and clinically meaningful improvement in ...

4.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(25)00866-9/abstract

mutated non-small-cell lung cancer (KRYSTAL-12): a ...

Adagrasib demonstrated a statistically significant improvement in progression-free survival over docetaxel in patients with previously treated ...

5.

cancernetwork.com

cancernetwork.com/view/adagrasib-pembrolizumab-yields-improved-survival-in-kras-g12c-mutated-nsclc

Adagrasib/Pembrolizumab Yields Improved Survival in ...

Results from the KRYSTAL-7 trial showed that efficacy was improved with adagrasib/pembrolizumab for KRAS G12C-mutated NSCLC.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9662862/

Activity of Adagrasib (MRTX849) in Brain Metastases

Patients with KRAS-mutant NSCLC demonstrated high propensity to develop BM (≥40%). Adagrasib penetrated into CSF and demonstrated tumor regression and extended ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20648

Clinical outcomes and safety profile of adagrasib in KRAS ...

Adagrasib showed a median overall survival (OS) of 14.74 months (95% CI: 12.06–17.42, I² = 40.4%) and progression-free survival (PFS) of 6.80 ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9697582/

Adagrasib: A landmark in the KRASG12C‐mutated NSCLC

We believe that the clinical outcome of adagrasib would be improved when applied at an earlier stage. The safety of adagrasib is acceptable. Although treatment‐ ...