Adagrasib for KRAS-Mutated Lung Cancer
Recruiting in Palo Alto (17 mi)
+114 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Mirati Therapeutics Inc.
Must not be taking: Steroids, KRAS inhibitors
Disqualifiers: Brain lesions, Pregnancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 Jurisdictions
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.12345
Is Adagrasib safe for humans?
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.12357
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.
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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
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Trial 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 (Small Molecule Drug)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: Adagrasib 600mg BIDExperimental Treatment1 Intervention
Adagrasib 600mg BID without regard to food
Group II: Adagrasib 400mg BIDExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Durham VA Medical CenterDurham, NC
VA North Texas Healthcare System/Dallas VA Medical CenterDallas, TX
Local Institution - 106Chicago, IL
Local Institution - 103Minneapolis, MN
More Trial Locations
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Who Is Running the Clinical Trial?
Mirati Therapeutics Inc.Lead Sponsor
References
Adagrasib: First Approval. [2023]Adagrasib (KRAZATI™) is an orally available, potent, irreversible, small molecule inhibitor of KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of solid tumours harbouring KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Adagrasib covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state, thereby preventing downstream signalling without affecting wild-type KRAS protein. In December 2022, adagrasib received its first approval in the USA for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic NSCLC (as determined by an FDA approved test) who have received ≥ 1 prior systemic therapy. It was approved under accelerated approval based on objective response rate and duration of response, and its continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). The drug is under regulatory review for NSCLC in the European Union and is in development for CRC in the US. Clinical studies of adagrasib in solid tumours, including CRC, are underway in several countries. This article summarizes the milestones in the development of adagrasib leading to this first approval for KRAS G12C-mutated locally advanced or metastatic NSCLC.
First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1). [2023]Label="PURPOSE">Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRASG12C. We report results from a phase I/IB study of adagrasib in non-small-cell lung cancer, colorectal cancer, and other solid tumors harboring the KRASG12C mutation.
Another KRAS Inhibitor Holds Its Own. [2021]According to the KRYSTAL-1 study, the KRASG12c inhibitor adagrasib, also known as MRTX849, is largely well tolerated and shows considerable efficacy in patients with non-small cell lung cancer harboring this mutation. The drug is also active, albeit more modestly, in colorectal cancer and several other solid tumor types.
Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]Two trials offer early evidence that adagrasib plus pembrolizumab is a safe and effective regimen for patients with newly diagnosed non-small cell lung cancer harboring a KRASG12C mutation. The overall response rate in one trial was 49%, and in the other it was 57%. The drug combination showed lower levels of liver toxicity than other combinations of checkpoint inhibitors and targeted therapies.
A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib. [2022]KRASG12C is one of the most common oncogenes in non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Historically, KRAS mutations have been difficult to target due to lack of binding sites and exceptionally high affinity for guanosine triphosphate/guanosine diphosphate (GTP/GDP). Recently, KRASG12C selective inhibitors have shown promising results in Phase I/II studies. Here we discuss the mechanism of action, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of adagrasib (MRTX849).
Adagrasib: a novel inhibitor for KRASG12C-mutated non-small-cell lung cancer. [2023]Adagrasib is a recently US FDA-approved novel KRASG12C targeted therapy with clinical efficacy in patients with advanced, pretreated KRASG12C-mutated non-small-cell lung cancer. KRYSTAL-I reported an objective response rate of 42.9% with median duration of response of 8.5 months. Treatment-related adverse events were primarily gastrointestinal and occurred in 97.4% of patients, with grade 3+ treatment-related adverse events occurring in 44.8% of patients. This review details the preclinical and clinical data for adagrasib in the treatment of non-small-cell lung cancer. We also outline practical clinical administration guidelines for this novel therapy, including management of toxicities. Finally, we discuss the implications of resistance mechanisms, summarize other KRASG12C inhibitors currently in development and outline future directions for adagrasib-based combination therapies.
Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. [2023]Patients with KRAS-mutant non-small cell lung cancer (NSCLC) with brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), a potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, and central nervous system penetration; however, BM-specific antitumor activity of KRASG12C inhibitors remains to be fully characterized.