Last reviewed 2026-04-20 · How we verify

Rozlytrek (entrectinib)

Rozlytrek works by blocking the activity of a specific protein called the nerve growth factor receptor.

Rozlytrek (entrectinib) is a small molecule developed by Genentech Inc that targets high affinity nerve growth factor receptor. It is approved for the treatment of ROS1-positive non-small cell lung cancer and solid tumors with neurotrophic receptor tyrosine kinase gene fusions. Rozlytrek is patented and has no generic manufacturers. It was approved by the FDA in 2019. Key safety considerations include potential side effects such as fatigue, nausea, and increased liver enzymes.

At a glance

Mechanism of action

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 IC50 values of 0.1 to nM. Entrectinib also inhibits JAK2 and TNK2 with IC50 values 5 nM. The major active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK.Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Entrectinib demonstrated in vitro and in vivo inhibition of cancer cell lines derived from multiple tumor types harboring NTRK, ROS1, and ALK fusion genes. Entrectinib demonstrated steady-state brain-to-plasma concentration ratios of 0.4 2.2 in multiple animal species (mice, rats

Approved indications

• Reactive oxygen species 1 positive non-small cell lung cancer
• Solid neoplasm with neurotrophic receptor tyrosine kinase gene fusion

Common side effects

• Fatigue
• Dyspnea
• Pleural effusion
• Sepsis
• Pulmonary embolism
• Respiratory failure
• Pyrexia
• Increased weight
• Lung infection
• Cognitive disorders
• Syncope
• Hypoxia

Key clinical trials

• Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options (PHASE1,PHASE2)
• Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors (PHASE2)
• A Rollover Study for Participants Previously Enrolled in a Genentech and/or F. Hoffman-La Roche Sponsored Study (PHASE3)
• A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (PHASE2,PHASE3)
• 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) (PHASE2)
• Tumor-agnostic Precision Immuno-oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study (PHASE2)
• 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) (PHASE3)
• A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) (PHASE2)

Patents

Primary sources

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Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Rozlytrek CI brief — competitive landscape report
• Rozlytrek updates RSS · CI watch RSS
• Roche portfolio CI