Adagrasib
Clinical data
Trade namesKrazati
Other namesMRTX-849
License data
Routes of
administration		By mouth
Drug classAntineoplastic agents
ATC code
Legal status
Legal status
Identifiers
  • {(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-{[(2S)-1methylpyrrolidin-2-yl]methoxy}-5,6,7,8tetrahydropyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop2-enoyl)piperazin-2-yl}acetonitrile
CAS Number
PubChem CID
DrugBank
UNII
KEGG
ECHA InfoCard100.329.928 Edit this at Wikidata
Chemical and physical data
FormulaC32H35ClFN7O2
Molar mass604.13 g·mol−1
3D model (JSmol)
  • CN1CCC[C@H]1COC2=NC3=C(CCN(C3)C4=CC=CC5=C4C(=CC=C5)Cl)C(=N2)N6CCN([C@H](C6)CC#N)C(=O)C(=C)F
  • InChI=1S/C32H35ClFN7O2/c1-21(34)31(42)41-17-16-40(18-23(41)11-13-35)30-25-12-15-39(28-10-4-7-22-6-3-9-26(33)29(22)28)19-27(25)36-32(37-30)43-20-24-8-5-14-38(24)2/h3-4,6-7,9-10,23-24H,1,5,8,11-12,14-20H2,2H3/t23-,24-/m0/s1
  • Key:PEMUGDMSUDYLHU-ZEQRLZLVSA-N

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. ^ a b c d e f g "Krazati- adagrasib tablet, coated". DailyMed. U.S. National Library of Medicine. 10 December 2021. Archived from the original on 14 January 2023. Retrieved 21 January 2023.
  2. ^ a b c d e f g h i "FDA grants accelerated approval to adagrasib for KRAS G12C-mutated NSCLC". U.S. Food and Drug Administration (FDA). 12 December 2022. Archived from the original on 14 December 2022. Retrieved 14 December 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  3. ^ a b "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.
  4. ^ "Accelerated Approval: Krazati (adagrasib) oral tablets" (PDF). U.S. Food and Drug Administration. 12 December 2022. Archived (PDF) from the original on 13 December 2022. Retrieved 13 December 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  5. ^ a b "Krazati: Pending EC decision". European Medicines Agency (EMA). 10 November 2023. Archived from the original on 13 November 2023. Retrieved 13 November 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ^ Hallin J, Engstrom LD, Hargis L, Calinisan A, Aranda R, Briere DM, et al. (January 2020). "The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients". Cancer Discovery. 10 (1): 54–71. doi:10.1158/2159-8290.CD-19-1167. PMC 6954325. PMID 31658955.
  7. ^ Fell JB, Fischer JP, Baer BR, Blake JF, Bouhana K, Briere DM, et al. (July 2020). "Identification of the Clinical Development Candidate MRTX849, a Covalent KRASG12C Inhibitor for the Treatment of Cancer". Journal of Medicinal Chemistry. 63 (13): 6679–6693. doi:10.1021/acs.jmedchem.9b02052. PMID 32250617.
  8. ^ Thein KZ, Biter AB, Hong DS (January 2021). "Therapeutics Targeting Mutant KRAS". Annual Review of Medicine. 72: 349–364. doi:10.1146/annurev-med-080819-033145. PMID 33138715. S2CID 226242453.
  9. ^ Christensen JG, Olson P, Briere T, Wiel C, Bergo MO (August 2020). "Targeting Krasg12c -mutant cancer with a mutation-specific inhibitor". Journal of Internal Medicine. 288 (2): 183–191. doi:10.1111/joim.13057. PMID 32176377.
  10. ^ Dunnett-Kane V, Nicola P, Blackhall F, Lindsay C (January 2021). "Mechanisms of Resistance to KRASG12C Inhibitors". Cancers. 13 (1): 151. doi:10.3390/cancers13010151. PMC 7795113. PMID 33466360.
  11. ^ Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, et al. (July 2022). "Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRASG12C Mutation". The New England Journal of Medicine. 387 (2): 120–131. doi:10.1056/NEJMoa2204619. PMID 35658005. S2CID 249352736.

External links

Intracellular chemotherapeutic agents / antineoplastic agents (L01)
Targeted cancer therapy / antineoplastic agents (L01)
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