Overview
Adagrasib (MRTX849) is an oral, small-molecule KRAS inhibitor developed by Mirati Therapeutics. KRAS mutations are highly common in cancer and account for approximately 85% of all RAS family mutations. However, the development of KRAS inhibitors has been challenging due to their high affinity for guanosine triphosphate (GTP) and guanosine diphosphate (GDP), as well as the lack of a clear binding pocket. Adagrasib targets KRAS, one of the most common KRAS mutations, at the cysteine 12 residue and inhibits KRAS-dependent signalling. In a phase I/IB clinical study that included patients with KRAS-mutated advanced solid tumors (NCT03785249), adagrasib exhibited anti-tumor activity. The phase II of the same study showed that in patients with KRAS-mutated non-small-cell lung cancer (NSCLC), adagrasib was efficient without new safety signals. In February 2022, the FDA accepted a new drug application (NDA) for adagrasib for the treatment of patients with previously treated KRAS–positive NSCLC. In December 2022, the FDA granted accelerated approval to adagrasib for the treatment of KRAS-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. Adagrasib joins sotorasib as another KRAS inhibitor approved by the FDA.
Indication
Adagrasib is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).
Associated Conditions
- Locally Advanced Non-Small Cell Lung Cancer
- Metastatic Non-Small Cell Lung Cancer
Research Report
Adagrasib (Krazati®): A Comprehensive Pharmacological and Clinical Monograph of a Covalent KRAS G12C Inhibitor
Executive Summary
Adagrasib, marketed as Krazati®, represents a significant therapeutic advancement in the field of precision oncology. It is an orally available, potent, and irreversible small-molecule inhibitor specifically designed to target the KRAS G12C mutant protein, an oncogenic driver long considered "undruggable".[1] Developed by Mirati Therapeutics and now part of the Bristol Myers Squibb portfolio, Adagrasib has successfully translated a deep understanding of molecular oncology into a clinically meaningful therapy for patients with specific, genetically defined cancers.
The drug has secured regulatory approvals in major markets for two distinct indications. In the United States, it is approved as a monotherapy for adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior systemic therapy. It is also approved in combination with cetuximab for adult patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.[3] These approvals were granted under accelerated pathways based on compelling efficacy data from the pivotal, multi-cohort KRYSTAL-1 clinical trial.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/03/13 | Phase 3 | Recruiting | |||
2025/01/30 | Phase 1 | Completed | |||
2025/01/08 | Phase 1 | Recruiting | |||
2024/07/11 | Phase 3 | Recruiting | |||
2024/05/14 | Phase 1 | Recruiting | |||
2024/02/08 | Phase 2 | Recruiting | Ryan Gentzler, MD | ||
2023/11/14 | Phase 1 | Recruiting | |||
2023/09/15 | Phase 1 | Terminated | |||
2023/09/07 | Phase 1 | Recruiting | |||
2023/09/06 | Phase 1 | Terminated |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Mirati Therapeutics, Inc | 80739-812 | ORAL | 200 mg in 1 1 | 12/10/2021 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 1/5/2024 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| KRAZATI TABLETS 200MG | N/A | N/A | N/A | 12/18/2024 |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| No Health Canada approvals found for this drug. | |||||
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| No CIMA AEMPS (Spain) approvals found for this drug. | |||||
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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