Adagrasib for KRAS-Mutated Lung Cancer

Recruiting at 176 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

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy of two dosing regimens of adagrasib (600 mg BID versus 400 mg BID) in patients with NSCLC with KRAS G12C mutation.

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.

What data supports the effectiveness of the drug Adagrasib for KRAS-mutated lung cancer?

Adagrasib has shown considerable effectiveness in treating non-small cell lung cancer with the KRAS G12C mutation, with studies reporting good response rates. It was approved in the USA based on its ability to shrink tumors and maintain this effect, and it is generally well tolerated by patients. ^{1 2 3 4 5}

Is Adagrasib safe for humans?

Adagrasib has been generally well tolerated in clinical trials, but most patients experienced some side effects, mainly related to the stomach and intestines. Serious side effects occurred in about 45% of patients. ^{1 2 3 5 6}

What makes the drug Adagrasib unique for treating KRAS-mutated lung cancer?

Adagrasib is unique because it is an oral drug that specifically targets the KRAS G12C mutation, which is common in non-small cell lung cancer and has been difficult to treat. It works by binding to the mutant protein and keeping it inactive, which helps stop cancer growth without affecting normal proteins. ^{1 2 3 5 7}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 (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, 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Adagrasib: First Approval. [2023]

2. United States 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). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Adagrasib: a novel inhibitor for KRASG12C-mutated non-small-cell lung cancer. [2023]

7. United States 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. [2023]