Chemistry:Adagrasib
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| Trade names | Krazati |
| Other names | MRTX-849 |
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| Routes of administration | By mouth |
| Drug class | Antineoplastic agents |
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| Formula | C32H35ClFN7O2 |
| Molar mass | 604.13 g·mol−1 |
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Adagrasib, sold under the brand name Krazati, is an anticancer medication used to treat non-small cell lung cancer.[1][2] Adagrasib is an inhibitor of the RAS GTPase family.[1] It is taken by mouth.[1] It is being developed by Mirati Therapeutics.[1][3]
The most common adverse reactions include diarrhea, nausea, fatigue, vomiting, musculoskeletal pain, hepatotoxicity, renal impairment, dyspnea, edema, decreased appetite, cough, pneumonia, dizziness, constipation, abdominal pain, and QTc interval prolongation.[2] The most common laboratory abnormalities include decreased lymphocytes, increased aspartate aminotransferase, decreased sodium, decreased hemoglobin, increased creatinine, decreased albumin, increased alanine aminotransferase, increased lipase, decreased platelets, decreased magnesium, and decreased potassium.[2]
It was approved for medical use in the United States in December 2022.[1][2][3]
Medical uses
Adagrasib is indicated for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, as determined by an FDA approved test, who have received at least one prior systemic therapy.[1][2][4]
History
Approval by the US Food and Drug Administration (FDA) was based on KRYSTAL-1, a multicenter, single-arm, open-label clinical trial (NCT03785249) which included participants with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations.[2] Efficacy was evaluated in 112 participants whose disease has progressed on or after platinum-based chemotherapy and an immune checkpoint inhibitor, given either concurrently or sequentially.[2]
The FDA granted the application for adagrasib fast-track, breakthrough therapy, and orphan drug designations.[2]
Society and culture
Legal status
In November 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency, following a re-examination procedure, adopted a positive opinion recommending the granting of a conditional marketing authorization for the medicinal product Krazati, intended for the treatment of people with KRAS G12C mutation non-small cell lung cancer.[5] The applicant for this medicinal product is Mirati Therapeutics B.V.[5]
Research
It is undergoing clinical trials.[6][7][8][9][10][11]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Krazati- adagrasib tablet, coated". DailyMed. U.S. National Library of Medicine. 10 December 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b8bf078-34c2-4f45-9012-38a8ac082b01.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC". 12 December 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-adagrasib-kras-g12c-mutated-nsclc.
This article incorporates text from this source, which is in the public domain.
- ↑ 3.0 3.1 "Mirati Therapeutics Announces U.S. FDA Accelerated Approval of Krazati (adagrasib) as a Targeted Treatment Option for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation" (Press release). Mirati Therapeutics Inc. 12 December 2022. Archived from the original on 13 December 2022. Retrieved 13 December 2022 – via MultiVu.
- ↑ "Accelerated Approval: Krazati (adagrasib) oral tablets". U.S. Food and Drug Administration. 12 December 2022. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/216340Orig1s000ltr.pdf. This article incorporates text from this source, which is in the public domain.
- ↑ 5.0 5.1 "Krazati: Pending EC decision". 10 November 2023. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/krazati. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ "The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients". Cancer Discovery 10 (1): 54–71. January 2020. doi:10.1158/2159-8290.CD-19-1167. PMID 31658955.
- ↑ "Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer". Journal of Medicinal Chemistry 63 (13): 6679–6693. July 2020. doi:10.1021/acs.jmedchem.9b02052. PMID 32250617.
- ↑ "Therapeutics Targeting Mutant KRAS". Annual Review of Medicine 72: 349–364. January 2021. doi:10.1146/annurev-med-080819-033145. PMID 33138715.
- ↑ "Targeting Krasg12c -mutant cancer with a mutation-specific inhibitor". Journal of Internal Medicine 288 (2): 183–191. August 2020. doi:10.1111/joim.13057. PMID 32176377.
- ↑ "Mechanisms of Resistance to KRASG12C Inhibitors". Cancers 13 (1): 151. January 2021. doi:10.3390/cancers13010151. PMID 33466360.
- ↑ "Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation". The New England Journal of Medicine 387 (2): 120–131. July 2022. doi:10.1056/NEJMoa2204619. PMID 35658005.
External links
- Clinical trial number NCT03785249 for "Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1" at ClinicalTrials.gov
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