Repotrectinib

Repotrectinib

Clinical data
Trade names	Augtyro
Other names	TPX-0005
AHFS/Drugs.com	Augtyro
License data	US DailyMed: Repotrectinib
Routes of administration	By mouth
Drug class	Tyrosine kinase inhibitor
ATC code	L01EX28 (WHO)
Legal status
Legal status	US: ℞-only[1] EU: Rx-only[2][3]
Identifiers
CAS Number	1802220-02-5
PubChem CID	135565923
DrugBank	DB16826
ChemSpider	64853849
UNII	08O3FQ4UNP
KEGG	D11454
ChEBI	CHEBI:229220
ChEMBL	ChEMBL4298138
PDB ligand	7GI (PDBe, RCSB PDB)
Chemical and physical data
Formula	C18H18FN5O2
Molar mass	355.373 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@H]1CNC(=O)C2=C3N=C(N[C@H](C)C4=CC(F)=CC=C4O1)C=CN3N=C2
InChI InChI=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 Key:FIKPXCOQUIZNHB-WDEREUQCSA-N

Repotrectinib, sold under the brand name Augtyro, is an anti-cancer medication used for the treatment of non-small cell lung cancer.^[1][4] It is taken by mouth.^[1] Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC.^[1]

The most common adverse reactions include dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.^[4]

Repotrectinib was approved for medical use in the United States in November 2023,^[4][5] and in the European Union in January 2025.^[2][3]

Repotrectinib is indicated for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer.^[1][4]

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.^[6][7]

The most common adverse reactions include dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.^[6]

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.^[4] 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.^[4]

The FDA granted the application for repotrectinib priority review, breakthrough therapy, and fast track designations.^[4]

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). ^[6][8] 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.^[6]

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).^[2] The applicant for this medicinal product is Bristol-Myers Squibb Pharma EEIG.^[2][9] Repotrectinib was approved for medical use in the European Union in January 2025.^[2][3]

• "Repotrectinib (Code C133821)". NCI Thesaurus. 25 September 2023. Retrieved 17 November 2023.