Entrectinib

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [ NTRK ] genes NTRK1, NTRK2, and NTRK3 , respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK) with IC 50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC 50 values > 5 nM.

• ROZLYTREK is a kinase inhibitor indicated for the treatment of: Adult patients with ROS1- positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ( 1.1 ) Adult and pediatric patients older than 1 month of age with solid tumors that: have a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.ICD-10: C34.90

• None. None.contraindicated

Select patients for treatment based on the presence of ROS1 rearrangement(s) or NTRK gene fusion. ( 2.1 ) Evaluate left ventricular ejection fraction, serum uric acid levels and QT interval and electrolytes prior to ROZLYTREK initiation. ( 2.2 ) Select appropriate dosage form: oral capsules, capsules prepared as an oral suspension or oral pellets. ( 2.3 ) Use capsules prepared as suspension for enteral tube administration. Do not use pellets for enteral tube administration. ( 2.3 ) Administer ROZLYTREK capsules, capsules prepared as a suspension, or pellets once daily, with or without food. ( 2.4 ) Adult Dosage for ROS1- Positive Non-Small Cell Lung Cancer: 600 mg orally once daily. ( 2.5 ) Adult and Pediatric Dosage for NTRK Gene Fusion-Positive Solid Tumors: Adults: 600 mg orally once daily. ( 2.6 ) Pediatric Patients: Recommended dosage is based on age and body surface area (BSA) as shown below. ( 2.6 ) Age Recommended Daily Dosage >6 months ≤0.50 m 2 : 300 mg/m 2 0.51 to 0.80 m 2 : 200 mg 0.81 to 1.10 m 2 : 300 mg 1.11 to 1.50 m 2 : 400 mg BSA ≥1.51 m 2 : 600 mg once daily >1 month to ≤6 months 250 mg/m 2 once daily Modify dosage of ROZLYTREK if coadministration with moderate or strong CYP3A inhibitors cannot be avoided. ( 2.8 ) See preparation and administration instructions. ( 2.9 ) 2.1 Patient Selection Select patients for the treatment of metastatic NSCLC with ROZLYTREK based on the presence of ROS1 rearrangement(s) in tumor or plasma specimens [see Clinical Studies (14.1) ] .

Congestive Heart Failure (CHF) : Assess left ventricular ejection fraction (LVEF) prior to initiation of ROZLYTREK. Monitor patients for clinical signs and symptoms of CHF. For patients with myocarditis, with or without a decreased ejection fraction, MRI or cardiac biopsy may be required to make the diagnosis. For new onset or worsening CHF, withhold ROZLYTREK, reassess LVEF and institute appropriate medical management. Reduce dose or permanently discontinue ROZLYTREK based on severity of CHF or worsening LVEF. ( 2.7 , 5.1 ) Central Nervous System (CNS) Effects: CNS adverse reactions including cognitive impairment, mood disorders, dizziness, and sleep disturbances can occur with ROZLYTREK. Withhold and then resume at same or reduced dose upon improvement or permanently discontinue ROZLYTREK based on severity. ( 2.7 , 5.2 ) Skeletal Fractures: ROZLYTREK increases the risk of fractures. Promptly evaluate patients with signs or symptoms of fractures. ( 5.3 ) Hepatotoxicity : Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue ROZLYTREK based on severity. If withheld, resume ROZLYTREK at same or reduced dose based on severity. ( 2.7 , 5.4 ) Hyperuricemia : Assess serum uric acid levels prior to initiation and periodically during treatment with ROZLYTREK. Monitor patients for signs and symptoms of hyperuricemia.

The following clinically significant adverse reactions are described elsewhere in the labeling: Congestive Heart Failure [see Warnings and Precautions (5.1) ] Central Nervous System Effects [see Warnings and Precautions (5.2) ] Skeletal Fractures [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Hyperuricemia [see Warnings and Precautions (5.5) ] QT Interval Prolongation [see Warnings and Precautions (5.6) ] Vision Disorders [see Warnings and Precautions (5.7) ] The most common adverse reactions (≥ 20%) were fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, increased weight, cough, vomiting, pyrexia, arthralgia, and vision disorders. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed 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. Data in WARNINGS AND PRECAUTIONS and below reflect exposure to ROZLYTREK in 355 patients, including 172 (48%) patients exposed for 6 months or longer and 84 (24%) patients exposed for 1 year or longer.

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) ] , ROZLYTREK can cause fetal harm when administered to a pregnant woman. There are no available data on ROZLYTREK use in pregnant women. Administration of entrectinib to pregnant rats during the period of organogenesis resulted in malformations at maternal exposures approximately 2.7 times the human exposure at the 600 mg dose (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 pharmacokinetics for entrectinib and its pharmacologically active major circulating metabolite M5 were characterized in adult patients with ROS1 -positive NSCLC, NTRK gene fusion-positive solid tumors, and healthy subjects. The pharmacokinetics of entrectinib and M5 are linear and are not dose-dependent or time-dependent.

• Aug 15, 2019NDANDA212725Genentech Inc
• Oct 20, 2023NDANDA218550Genentech Inc

1. 1Off Label Use16710%
2. 2Dizziness1499.2%
3. 3Death1348.3%
4. 4Disease Progression1157.1%
5. 5Taste Disorder704.3%
6. 6Drug Ineffective694.3%
7. 7No Adverse Event694.3%
8. 8Constipation654.0%
9. 9Fatigue623.8%
10. 10Blood Creatinine Increased603.7%
11. 11Diarrhoea593.7%
12. 12Nausea583.6%
13. 13Renal Impairment573.5%
14. 14Weight Increased523.2%
15. 15Cardiac Failure472.9%

The 10 most recently updated of 44 ClinicalTrials.gov registrations naming Entrectinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Rollover Study for Participants Previously Enrolled in a Genentech and/or F. Hoffman-La Roche Sponsored Study
  Recruiting · Phase 3 · Interventional · 100 enrolled · Hoffmann-La Roche
  NCT05862285updated 2026-06-12
• A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC)
  Recruiting · Phase 2 · Interventional · 99 enrolled · Genentech, Inc.
  NCT04302025updated 2026-06-09
• A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 1,000 enrolled · Hoffmann-La Roche
  NCT03178552updated 2026-06-05
• A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases
  Active not recruiting · Phase 3 · Interventional · 220 enrolled · Hoffmann-La Roche
  NCT04603807updated 2026-05-28
• Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
  Active not recruiting · Phase 2 · Interventional · 534 enrolled · Hoffmann-La Roche
  NCT02568267updated 2026-05-27
• Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors
  Recruiting · Phase 2 · Interventional · 52 enrolled · St. Jude Children's Research Hospital
  NCT06528691updated 2026-05-13
• Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study
  Active not recruiting · Phase 2 · Interventional · 920 enrolled · Hoffmann-La Roche
  NCT04589845updated 2026-05-08
• A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)
  Active not recruiting · Phase 3 · Interventional · 68 enrolled · Hoffmann-La Roche
  NCT05170204updated 2026-05-06
• Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
  Active not recruiting · Phase 1 · Interventional · 13 enrolled · OHSU Knight Cancer Institute
  NCT05396859updated 2026-04-27
• Genetic Testing in Guiding Treatment for Patients With Brain Metastases
  Active not recruiting · Phase 2 · Interventional · 50 enrolled · Alliance for Clinical Trials in Oncology
  NCT03994796updated 2026-04-13

Frequently asked questions

How does Entrectinib work?

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [ NTRK ] genes NTRK1, NTRK2, and NTRK3 , respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK) with IC 50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC 50 values > 5 nM.

What is Entrectinib used for?

According to FDA labeling, Entrectinib carries indications including: ROZLYTREK is a kinase inhibitor indicated for the treatment of: Adult patients with ROS1- positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ( 1.1 ) Adult and pediatric patients older than 1 month of age with solid tumors that: have a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Entrectinib?

Entrectinib is classified as Other protein kinase inhibitors, Protein Kinase Inhibitors, Receptor Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Entrectinib?

Entrectinib is marketed under brand names including Rozlytrek.

What are the contraindications for Entrectinib?

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