Repotrectinib
{{Short description|Medication}}
{{Use American English|date=November 2023}}
{{Use dmy dates|date=June 2024}}
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{{Infobox drug
| image = Repotrectinib.svg
| image2 = Repotrectinib 7VKN.png
| alt =
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| pronounce =
| tradename = Augtyro
| Drugs.com = {{drugs.com|parent|Augtyro}}
| MedlinePlus =
| DailyMedID = Repotrectinib
| pregnancy_AU =
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| routes_of_administration = By mouth
| class = Tyrosine kinase inhibitor
| ATC_prefix = L01
| ATC_suffix = EX28
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| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title=Register of Innovative Drugs | website=Health Canada | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/register-innovative-drugs.html | access-date=23 May 2025}}
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| legal_US = Rx-only
| legal_EU = Rx-only
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| CAS_number = 1802220-02-5
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| PubChem = 135565923
| IUPHAR_ligand =
| DrugBank = DB16826
| ChemSpiderID = 64853849
| UNII = 08O3FQ4UNP
| KEGG = D11454
| ChEBI = 229220
| ChEMBL = 4298138
| NIAID_ChemDB =
| PDB_ligand = 7GI
| synonyms = TPX-0005
| IUPAC_name =
| C = 18 | H = 18 | F = 1 | N = 5 | O = 2
| SMILES = C[C@H]1CNC(=O)C2=C3N=C(N[C@H](C)C4=CC(F)=CC=C4O1)C=CN3N=C2
| StdInChI = 1S/C18H18FN5O2/c1-10-8-20-18(25)14-9-21-24-6-5-16(23-17(14)24)22-11(2)13-7-12(19)3-4-15(13)26-10/h3-7,9-11H,8H2,1-2H3,(H,20,25)(H,22,23)/t10-,11+/m0/s1
| StdInChI_comment =
| StdInChIKey = FIKPXCOQUIZNHB-WDEREUQCSA-N
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Repotrectinib, sold under the brand name Augtyro, is an anti-cancer medication used for the treatment of non-small cell lung cancer. It is taken by mouth. Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC.
The most common adverse reactions include dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.
Repotrectinib was approved for medical use in the United States in November 2023,{{cite web | title=FDA approves repotrectinib for ROS1-positive non-small cell lung cancer | website=U.S. Food and Drug Administration (FDA) | date=15 November 2023 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer | access-date=17 November 2023 | archive-date=16 November 2023 | archive-url=https://web.archive.org/web/20231116191134/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer | url-status=dead }} {{PD-notice}}{{cite press release | title=U.S. Food and Drug Administration Approves Augtyro (repotrectinib), a Next-Generation Tyrosine Kinase Inhibitor (TKI), for the Treatment of Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC) | publisher=Bristol Myers Squibb | via=Business Wire | date=16 November 2023 | url=https://www.businesswire.com/news/home/20231115632242/en/ | access-date=17 November 2023 | archive-date=16 November 2023 | archive-url=https://web.archive.org/web/20231116192414/https://www.businesswire.com/news/home/20231115632242/en | url-status=live }} and in the European Union in January 2025.
Medical uses
Repotrectinib is indicated for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer.
In June 2024, the US Food and Drug Administration (FDA) expanded the indication to include the treatment of people twelve years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory alternative therapy.{{cite web | title=Cancer Accelerated Approvals | website=U.S. Food and Drug Administration (FDA) | date=1 October 2024 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals | access-date=6 December 2024}}
Side effects
History
Approval by the US Food and Drug Administration (FDA) was based on TRIDENT-1, a global, multicenter, single-arm, open-label, multi-cohort clinical trial (NCT03093116) which included participants with ROS1-positive locally advanced or metastatic non-small cell lung cancer. Efficacy was evaluated in 71 ROS1 tyrosine kinase inhibitor-naïve participants who received up to one prior line of platinum-based chemotherapy and/or immunotherapy and 56 participants who received one prior ROS1 tyrosine kinase inhibitor with no prior platinum-based chemotherapy or immunotherapy.
The FDA granted the application for repotrectinib priority review, breakthrough therapy, and fast track designations.
= Clinical trials =
== TRIDENT-1 ==
Efficacy was evaluated in TRIDENT-1 (NCT03093116), a multicenter, single-arm, open-label, multi-cohort trial in 88 adult participants with locally advanced or metastatic neurotrophic tyrosine receptor kinase gene fusion-positive solid tumors who had either received a prior TRK tyrosine kinase inhibitor (TKI) (n=48) or were TKI-naïve (n=40). {{cite web |date=13 June 2024 |title=FDA grants accelerated approval to repotrectinib for adult and pediatric participants with neurotrophic tyrosine receptor kinase gene fusion-positive solid tumors |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive |access-date=13 June 2024 |website=U.S. Food and Drug Administration |archive-date=13 June 2024 |archive-url=https://web.archive.org/web/20240613185259/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-repotrectinib-adult-and-pediatric-patients-ntrk-gene-fusion-positive |url-status=live }} {{PD-notice}}{{Cite report |url=https://clinicaltrials.gov/study/NCT03093116 |title=A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1) |last=Turning Point Therapeutics, Inc. |date=5 February 2024 |publisher=clinicaltrials.gov |issue=NCT03093116 |access-date=18 June 2024 |archive-date=18 June 2024 |archive-url=https://web.archive.org/web/20240618080337/https://clinicaltrials.gov/study/NCT03093116 |url-status=live }} All participants were assessed for central nervous (CNS) lesions at baseline, and patients with symptomatic brain metastases were excluded. Tumor assessments were performed every eight weeks.
Society and culture
= Legal status =
In November 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Augtyro, intended for the treatment of people whose solid tumors have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, or people with ROS1-positive advanced non-small cell lung cancer (NSCLC). The applicant for this medicinal product is Bristol-Myers Squibb Pharma EEIG.{{cite web | title=Augtyro EPAR | website=European Medicines Agency (EMA) | date=14 November 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/augtyro | access-date=16 November 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.{{cite web | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 11-14 November 2024 | website=European Medicines Agency (EMA) | date=15 November 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-11-14-november-2024 | access-date=16 November 2024}} Repotrectinib was authorized for medical use in the European Union in January 2025.{{cite web | title=Augtyro PI | website=Union Register of medicinal products | date=14 January 2025 | url=https://ec.europa.eu/health/documents/community-register/html/h1883.htm | access-date=16 January 2025}}
References
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Further reading
{{refbegin}}
- {{cite journal | vauthors = Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J, Zhai D, Deng W, Huang Z, Rogers E, Liu J, Whitten J, Lim JK, Stopatschinskaja S, Hyman DM, Doebele RC, Cui JJ, Shaw AT | title = Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations | journal = Cancer Discovery | volume = 8 | issue = 10 | pages = 1227–1236 | date = October 2018 | pmid = 30093503 | doi = 10.1158/2159-8290.CD-18-0484 | doi-access = free }}
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External links
- {{cite web | title=Repotrectinib (Code C133821) | website=NCI Thesaurus | date=25 September 2023 | url=https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C133821 | access-date=17 November 2023}}
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Category:Drugs developed by Bristol Myers Squibb
Category:Tyrosine kinase inhibitors
Category:Heterocyclic compounds with 4 rings