Repotrectinib

Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 or TRK domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation.

• AUGTYRO is a kinase inhibitor indicated for the treatment of • adult patients with locally advanced or metastatic ROS1- positive non-small cell lung cancer (NSCLC). ( 1.1 ) • adult and pediatric patients 12 years of age and older with solid tumors that: • have a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion and • are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity.ICD-10: C34.90

• None. None.contraindicated

• Select patients for the treatment of locally advanced or metastatic NSCLC based on the presence of ROS1 rearrangement(s) in tumor specimens. ( 2.1 ) • Select patients for treatment of locally advanced or metastatic solid tumors based on the presence of an NTRK gene fusion. ( 2.1 ) • Recommended Dosage : 160 mg orally once daily for 14 days, then increase to 160 mg twice daily, with or without food. ( 2.4 ) 2.1 Patient Selection NSCLC Select patients for the treatment of locally advanced or metastatic NSCLC with AUGTYRO based on the presence of ROS1 rearrangement(s) in tumor specimens [see Clinical Studies (14.1) ] . An FDA-approved test to detect ROS1 rearrangements for selecting patients for treatment with AUGTYRO is not currently available. Solid Tumors Select patients for the treatment of solid tumors with AUGTYRO based on the presence of NTRK1/2/3 rearrangements in tumor specimens [see Clinical Studies ( 14.2 )] . An FDA-approved test to detect NTRK1/2/3 rearrangements for selecting patients for treatment with AUGTYRO is not currently available. • In patients with secretory breast cancer or mammary analogue secretory cancer, consider treatment without confirmation of NTRK rearrangements in tumor specimens. 2.2 Important Information Prior to Initiating AUGTYRO Prior to initiating AUGTYRO, discontinue strong and moderate CYP3A inhibitors for 3 to 5 elimination half-lives of the CYP3A inhibitor [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ].

• Central Nervous System (CNS) Effects: Can cause CNS adverse reactions including dizziness, ataxia, and cognitive impairment. Withhold and then resume at same or reduced dose upon improvement, or permanently discontinue AUGTYRO based on severity. ( 5.1 ) • Interstitial Lung Disease (ILD)/Pneumonitis: Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed. ( 5.2 ) • Hepatotoxicity: Monitor liver function tests every 2 weeks during the first month of treatment, and as clinically indicated thereafter. Based on severity, withhold and then resume at same or reduced dose, or permanently discontinue. ( 5.3 ) • Myalgia with Creatine Phosphokinase (CPK) Elevation: Monitor serum CPK levels during treatment in patients reporting unexplained muscle pain, tenderness, or weakness. Based on severity, withhold and resume at same or reduced dose upon improvement. ( 5.4 ) • Hyperuricemia: Monitor serum uric acid levels prior to initiating and periodically during treatment. Initiate treatment with urate-lowering medications as clinically indicated. Withhold and resume at same or reduced dose, or permanently discontinue based on severity. ( 5.5 ) • Skeletal Fractures: Promptly evaluate patients with signs or symptoms (e.g., pain, changes in mobility, deformity) of fractures. ( 5.6 ) • Embryo-Fetal Toxicity: Can cause fetal harm.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Central Nervous System Adverse Reactions [see Warnings and Precautions (5.1) ] • Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2) ] • Hepatotoxicity [see Warnings and Precautions (5.3) ] • Myalgia with Creatine Phosphokinase Elevation [see Warnings and Precautions (5.4) ] • Hyperuricemia [see Warnings and Precautions (5.5) ] • Skeletal Fractures [see Warnings and Precautions (5.6) ] • Embryo-Fetal Toxicity [see Warnings and Precautions (5.7) ] The most common adverse reactions (≥20%) were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea. ( 6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates reported in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to AUGTYRO in 426 patients with ROS1 -positive NSCLC (n=320), NTRK1/2/3 -positive solid tumors (n=104), or other solid tumors (n=2) in TRIDENT-1.

• Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on literature reports in humans with congenital mutations leading to changes in TRK signaling, findings from animal studies, and its mechanism of action [see Clinical Pharmacology (12.1) ], AUGTYRO can cause fetal harm when administered to a pregnant woman. There are no available data on AUGTYRO use in pregnant women. Oral administration of repotrectinib to pregnant rats during the period of organogenesis resulted in fetal malformations at doses approximately 0.3 times the recommended dose of 160 mg twice daily based on BSA (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Published reports of individuals with congenital mutations in TRK pathway proteins suggest that decreases in TRK-mediated signaling are correlated with obesity, developmental delays, cognitive impairment, insensitivity to pain, and anhidrosis.

Metabolism

The geometric mean (CV%) of repotrectinib steady state peak concentration (C max,ss ) is 713 (32.5%) ng/mL and the area under the time concentration curve (AUC 0-24h,ss ) is 7210 (40.1%) ng•h/mL following the approved recommended twice daily dosage in patients with cancer. Repotrectinib C max and AUC 0-inf increases approximately dose proportional (but less than linear with estimated slopes of 0.78 and 0.70, respectively) over the single dose range of 40 mg to 240 mg (0.25 to 1.5 times the approved recommended dosage).

• Nov 15, 2023NDANDA218213Bristol

1. 1Dizziness3816%
2. 2Death2310.0%
3. 3Nausea187.8%
4. 4Neuropathy Peripheral166.9%
5. 5Fatigue135.6%
6. 6Off Label Use135.6%
7. 7Adverse Event125.2%
8. 8Muscular Weakness104.3%
9. 9Pain104.3%
10. 10Paraesthesia104.3%
11. 11Balance Disorder93.9%
12. 12Gait Disturbance93.9%
13. 13Pulmonary Embolism93.9%
14. 14Anaemia83.5%
15. 15Hospitalisation83.5%

The 10 most recently updated of 16 ClinicalTrials.gov registrations naming Repotrectinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Repotrectinib in Combination With Chemotherapy in Children and Young Adults With Solid Tumor Cancer
  Recruiting · Phase 1 · Phase 2 · Interventional · 77 enrolled · Memorial Sloan Kettering Cancer Center
  NCT05004116updated 2026-06-04
• A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements
  Recruiting · Phase 1 · Phase 2 · Interventional · 500 enrolled · Turning Point Therapeutics, Inc.
  NCT03093116updated 2026-05-27
• Repotrectinib Post-Marketing Surveillance in Korean Patients With ROS1-Positive Non-Small Cell Lung Cancer (NSCLC) or Solid Tumors Harboring a Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusion
  Not yet recruiting · Observational · 10 enrolled · Bristol-Myers Squibb
  NCT07599007updated 2026-05-20
• Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
  Recruiting · Phase 2 · Interventional · 30 enrolled · Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
  NCT06552234updated 2026-04-13
• Study to Evaluate the Effect of Repotrectinib on the Drug Levels of Transporter and CYP P450 Probe Substrates in Healthy Adult Participants
  Completed · Phase 1 · Interventional · 30 enrolled · Bristol-Myers Squibb
  NCT07223671updated 2026-03-27
• REPotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain mEtastasis
  Recruiting · Phase 2 · Interventional · 20 enrolled · MedSIR
  NCT06315010updated 2026-02-25
• Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)
  Terminated · Phase 2 · Interventional · 6 enrolled · M.D. Anderson Cancer Center
  NCT06408168updated 2026-01-05
• A Study of Repotrectinib Versus Crizotinib in Participants With Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
  Active not recruiting · Phase 3 · Interventional · 190 enrolled · Bristol-Myers Squibb
  NCT06140836updated 2025-11-21
• A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
  Recruiting · Phase 1 · Phase 2 · Interventional · 75 enrolled · Turning Point Therapeutics, Inc.
  NCT04094610updated 2025-11-19
• A Study to Assess the Drug Levels of Repotrectinib in Healthy Participants and Participants With Moderate and Severe Hepatic Impairment
  Completed · Phase 1 · Interventional · 18 enrolled · Bristol-Myers Squibb
  NCT06352528updated 2025-10-06

Frequently asked questions

How does Repotrectinib work?

Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 or TRK domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation.

What is Repotrectinib used for?

According to FDA labeling, Repotrectinib carries indications including: AUGTYRO is a kinase inhibitor indicated for the treatment of • adult patients with locally advanced or metastatic ROS1- positive non-small cell lung cancer (NSCLC). ( 1.1 ) • adult and pediatric patients 12 years of age and older with solid tumors that: • have a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion and • are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Repotrectinib?

Repotrectinib is classified as Other protein kinase inhibitors, Kinase Inhibitor, Cytochrome P450 3A4 Inducers, Proto-Oncogene Tyrosine-Protein Kinase ROS1 Inhibitors, Receptor Tyrosine Kinase Inhibitors, Tropomyosin Receptor Tyrosine Kinase A Inhibitors, Tropomyosin Receptor Tyrosine Kinase B Inhibitors, Tropomyosin Receptor Tyrosine Kinase C Inhibitors.

What are the brand names for Repotrectinib?

Repotrectinib is marketed under brand names including Augtyro.

What are the contraindications for Repotrectinib?

Repotrectinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.