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	None;
Legal status
Legal status	US: ℞-only;
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]^[2] 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.^[2]

Repotrectinib was approved for medical use in the United States in November 2023.^[2]^[3]

Medical uses

Repotrectinib is indicated for the treatment of adults with locally advanced or metastatic ROS1-positive non-small cell lung cancer.^[1]^[2]

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.^[4]^[5]

Side effects

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

History

Approval by the US 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.^[2] 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.^[2]

The FDA granted the application for repotrectinib priority review, breakthrough therapy, and fast track designations.^[2]

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). ^[4]^[6] 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.^[4]

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).^[7] The applicant for this medicinal product is Bristol-Myers Squibb Pharma EEIG.^[7]^[8]

References

^ ^a ^b ^c ^d ^e "Augtyro- repotrectinib capsule". DailyMed. 15 November 2023. Archived from the original on 12 December 2023. Retrieved 12 December 2023.
^ ^a ^b ^c ^d ^e ^f ^g "FDA approves repotrectinib for ROS1-positive non-small cell lung cancer". U.S. Food and Drug Administration (FDA). 15 November 2023. Archived from the original on 16 November 2023. Retrieved 17 November 2023. This article incorporates text from this source, which is in the public domain.
^ "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)" (Press release). Bristol Myers Squibb. 16 November 2023. Archived from the original on 16 November 2023. Retrieved 17 November 2023 – via Business Wire.
^ ^a ^b ^c ^d "FDA grants accelerated approval to repotrectinib for adult and pediatric participants with neurotrophic tyrosine receptor kinase gene fusion-positive solid tumors". U.S. Food and Drug Administration. 13 June 2024. Archived from the original on 13 June 2024. Retrieved 13 June 2024. This article incorporates text from this source, which is in the public domain.
^ "Cancer Accelerated Approvals". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 6 December 2024.
^ Turning Point Therapeutics, Inc. (5 February 2024). 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) (Report). clinicaltrials.gov. Archived from the original on 18 June 2024. Retrieved 18 June 2024.
^ ^a ^b "Augtyro EPAR". European Medicines Agency (EMA). 14 November 2024. Retrieved 16 November 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 11-14 November 2024". European Medicines Agency (EMA). 15 November 2024. Retrieved 16 November 2024.

External links

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

[Augtyro_FDA_label-1] "Augtyro- repotrectinib capsule". DailyMed. 15 November 2023. Archived from the original on 12 December 2023. Retrieved 12 December 2023.

[FDA_repotrectinib-2] ^ ^a ^b ^c ^d ^e ^f ^g "FDA approves repotrectinib for ROS1-positive non-small cell lung cancer". U.S. Food and Drug Administration (FDA). 15 November 2023. Archived from the original on 16 November 2023. Retrieved 17 November 2023. This article incorporates text from this source, which is in the public domain.

[3] "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)" (Press release). Bristol Myers Squibb. 16 November 2023. Archived from the original on 16 November 2023. Retrieved 17 November 2023 – via Business Wire.

[FDA_20240613-4] "FDA grants accelerated approval to repotrectinib for adult and pediatric participants with neurotrophic tyrosine receptor kinase gene fusion-positive solid tumors". U.S. Food and Drug Administration. 13 June 2024. Archived from the original on 13 June 2024. Retrieved 13 June 2024. This article incorporates text from this source, which is in the public domain.

[5] "Cancer Accelerated Approvals". U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 6 December 2024.

[6] Turning Point Therapeutics, Inc. (5 February 2024). 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) (Report). clinicaltrials.gov. Archived from the original on 18 June 2024. Retrieved 18 June 2024.

[Augtyro_EPAR-7] "Augtyro EPAR". European Medicines Agency (EMA). 14 November 2024. Retrieved 16 November 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[8] "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 11-14 November 2024". European Medicines Agency (EMA). 15 November 2024. Retrieved 16 November 2024.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]