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DRUG CLASS:

Trk inhibitor

29d
Trial initiation date
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Augtyro (repotrectinib)
1m
Tissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions. (PubMed, Cancers (Basel))
Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases...More recently, the FDA approved the use of repotrectinib, a second-generation TRK inhibitor, in patients with NTRK fusions, based on data suggesting clinical efficacy and safety, which could offer another tool for the treatment of NTRK-altered cancers. In this review, we summarize the current evidence related to the use of TRK inhibitors in the tissue-agnostic setting. We also elaborate on the safety profiles and resistance mechanisms from a practical perspective.
Review • Journal • Pan tumor
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
1m
Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer. (PubMed, Clin Transl Med)
The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.
Review • Journal
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 fusion • ROS1 positive • ROS1 rearrangement • ROS1 G2032R
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
2ms
Enrollment open
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Augtyro (repotrectinib)
2ms
Application of newly developed and validated UPLC-MS/MS method for pharmacokinetic study of ROS1/NTRK inhibitor taletrectinib in beagle dog plasma. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci)
The procedure was then applied to quantify taletrectinib in beagle dog plasma after oral and intravenous doses and achieved success. The obtained pharmacokinetic parameters indicated high bioavailability of taletrectinib (>85 %) and extensive tissue distribution (>40 L/kg).
PK/PD data • Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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taletrectinib (AB-106)
2ms
Current Landscape of NTRK Inhibition for Pediatric CNS Tumors. (PubMed, CNS Drugs)
The use of larotrectinib and entrectinib in the relapsed setting for pediatric CNS tumors has resulted in rapid and robust responses in an important fraction of patients. As these agents are more broadly used, resistance will become a more pervasive issue and strategies will need to be determined for this scenario. This article summarizes the current status of NTRK inhibitors for pediatric CNS tumors and discusses the opportunities and challenges of their expanding use in the future.
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK positive • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
2ms
ROS1-rearranged non-small cell lung cancer: Understanding biology and optimizing management in the era of new approvals. (PubMed, Curr Probl Cancer)
Multiple tyrosine kinase inhibitors (TKIs) are now available for the effective treatment of ROS1-rearranged NSCLC in the metastatic setting including crizotinib, entrectinib, and repotrectinib as first-line therapy options. In addition, newer targeted therapies with increased selectivity for ROS1 over other targets are also emerging. As treatment of the disease continues to evolve, understanding the clinical course of patients with ROS1-rearranged NSCLC as well as the data supporting the latest therapy options is key to timely, effective, and longitudinal care.
Review • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ROS1 rearrangement
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
2ms
BPI-28592 as a novel second generation inhibitor for NTRK fusion tumors. (PubMed, NPJ Precis Oncol)
Clinically, BPI-28592 achieved a complete response in a patient with malignant melanoma carrying an AP3S2-NTRK3 fusion (Clinicaltrials. gov identifier: NCT05302843).
Journal
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK3 fusion • NTRK fusion
3ms
Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study). (PubMed, Curr Oncol)
Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.
Retrospective data • Journal • Real-world evidence • Real-world
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
Advances and future directions in ROS1 fusion-positive lung cancer. (PubMed, Oncologist)
The preferred Food and Drug Administration-approved first-line therapies include crizotinib, entrectinib, and repotrectinib, and currently, selection amongst these options requires consideration of the systemic and CNS efficacy, tolerability, and access to therapy. Herein, we describe a practical approach for the selection of initial and subsequent therapies for metastatic ROS1+ NSCLC based on these clinical considerations. Additionally, we explore the evolving evidence for the optimal treatment of earlier-stage, non-metastatic ROS1+ NSCLC, while, in parallel, highlighting future research directions with the goal of continuing to build on the tremendous progress in the management of ROS1+ NSCLC and ultimately improving the longevity and well-being of people living with this disease.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
3ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
3ms
A Study to Evaluate the Efficacy and Safety of TL118 in Solid Tumors Patients (clinicaltrials.gov)
P2, N=60, Recruiting, Teligene US | Not yet recruiting --> Recruiting | Trial completion date: Dec 2025 --> Apr 2026 | Initiation date: May 2024 --> Mar 2023 | Trial primary completion date: Dec 2025 --> Aug 2025
Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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TL118
4ms
Pleomorphic xanthoastrocytoma with NTRK fusion presenting as spontaneous intracranial hemorrhage-case report and literature review. (PubMed, Front Pediatr)
To date, there are very few pediatric cases of PXA that present with spontaneous pICH and whose tumors have undergone thorough molecular testing. Our patient's journey highlights the role of a dedicated multidisciplinary neuro-oncology team to guide optimal treatment.
Review • Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NTRK (Neurotrophic receptor tyrosine kinase)
4ms
L2086F Mutant ROS1-Rearranged NSCLC Resistant to Repotrectinib Responds to Cabozantinib: A Case Report. (PubMed, JTO Clin Res Rep)
Here, we report a case of a patient who was heavily pretreated, with advanced L1951R and L2026M mutated ROS1-rearranged NSCLC, who initially responded to repotrectinib but later developed further on-target resistance with the emergence of an L2086F mutation. The disease then responded to cabozantinib, a separate class of ROS1 TKI with preclinical activity against L2086F.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Cabometyx (cabozantinib tablet) • Augtyro (repotrectinib)
4ms
The mutual interplay between NTRK fusion genes and human papillomavirus infection in cervical cancer progression (Review). (PubMed, Mol Clin Oncol)
Moreover, the present study discussed the clinical features, histopathological examinations, treatment procedures and follow-up outcomes of NTRK-fusion gene-positive cervical cancer. The present review may help in the understanding of the management and treatment of such rare, lethal and resistant cervical cancers.
Review • Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
4ms
TRKing down drug resistance in NTRK fusion-positive cancers†. (PubMed, J Pathol)
Prolonged exposure to escalating concentrations of the tyrosine kinase inhibitor, entrectinib, ultimately led to the occurrence of resistant clones that harbored an inactivating mutation in the NF2 gene, not previously described in this context, accompanied by increased PI3K/AKT/mTOR and Ras/Raf/MEK/ERK signaling. Finally, an inhibitor screen identified, among others, MEK and mTOR inhibitors as potential combination agents.
Journal
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NF2 (Neurofibromin 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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Rozlytrek (entrectinib)
4ms
Nonsmall-cell lung cancer treatment: current status of drug repurposing and nanoparticle-based drug delivery systems. (PubMed, Turk J Biol)
First, the molecular mechanisms of Food and Drug Administration (FDA)-approved drugs for NSCLC, including ROS1 tyrosine kinase inhibitors (TKI) like repotrectinib, approved in November 2023, are detailed. Further, in vitro studies employing a combination strategy of drug repurposing and NP-based drug delivery systems as a treatment approach against NSCLC are listed. It includes the latest study on nanoparticle-based drug delivery systems loaded with repurposed drugs.
Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Augtyro (repotrectinib)
4ms
Discovery of novel indazole derivatives as second-generation TRK inhibitors. (PubMed, Eur J Med Chem)
NTRK fusion-positive cancers can be treated with the first-generation TRK inhibitors, larotrectinib and entrectinib...And the inhibitory effect against TRKAG667C (IC50 = 9.9 nM) was better than that of selitrectinib (IC50 = 113.1 nM). Further, compound B31 exhibited moderate kinase selectivity and excellent plasma stability (t1/2 > 480 min). In vivo pharmacokinetic studies in Sprague-Dawley rats showed that B31 had acceptable pharmacokinetic properties.
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • selitrectinib (BAY 2731954)
4ms
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors. (PubMed, Acta Neuropathol Commun)
Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.
Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MDM4 (The mouse double minute 4) • TPM3 (Tropomyosin 3) • TFG (Trafficking From ER To Golgi Regulator) • FKBP15 (FKBP Prolyl Isomerase 15) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like) • GKAP1 (G Kinase Anchoring Protein 1) • KIF5A (Kinesin Family Member 5A)
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carboplatin • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib) • thiotepa
4ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
5ms
New P1 trial
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Augtyro (repotrectinib)
5ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
5ms
Journal • Metastases
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NTRK (Neurotrophic receptor tyrosine kinase)
5ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
5ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
5ms
Efficacy and safety of NTRK inhibitors in patients with NTRK fusion-positive lung and thyroid cancers. (PubMed, Clin Adv Hematol Oncol)
Larotrectinib and entrectinib also produce robust and durable responses in NTRK fusion-positive thyroid cancer that is refractory to radioactive iodine. Second-generation TRK inhibitors that have been designed to overcome acquired resistance are under investigation.
Review • Journal • IO biomarker
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NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers. (PubMed, J Manag Care Spec Pharm)
Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.
Retrospective data • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
A case of breast secretory carcinoma metastasis to the lung in which NTRK fusion gene was confirmed by cancer genome profiling (JBCS 2024)
Currently, two drugs, entrectinib and larotrectinib, are approved for use in Japan, and they are planned to be used in this case in the event of recurrence. [Summary] Cancer genome profiling was performed on a very rare case of lung metastasis from breast secretory carcinoma, and the ETV6-NTRK fusion gene was confirmed
Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
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PD-L1 IHC 22C3 pharmDx
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
5ms
Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan. (PubMed, Cancer Med)
NTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
5ms
Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumours with on-target resistance to first-generation agents. (PubMed, Br J Cancer)
Our data identifies zurletrectinib as a novel, highly potent next-generation TRK inhibitor with stronger in vivo brain penetration and intracranial activity than other next-generation agents.
Journal
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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Vitrakvi (larotrectinib) • Augtyro (repotrectinib) • zurletrectinib (ICP-723) • selitrectinib (BAY 2731954)
5ms
FDA Approval Summary: Repotrectinib for locally advanced or metastatic ROS1-positive non-small cell lung cancer. (PubMed, Clin Cancer Res)
The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs.
FDA event • Journal • Metastases
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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Augtyro (repotrectinib)
5ms
Feasibility of Two-Step Approach for Screening NTRK Fusion in Two Major Subtypes of Non-Small Cell Lung Cancer Within a Large Cohort. (PubMed, Hum Pathol)
We recommend using IHC with strict criteria to screen NTRK fusion in LADC rather than LSCC, confirmed by RNA-based NGS directly. When the NGS results are inconclusive, FISH validation is necessary.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • TPM3 (Tropomyosin 3) • SQSTM1 (Sequestosome 1) • NTRK (Neurotrophic receptor tyrosine kinase) • XRCC1 (X-Ray Repair Cross Complementing 1)
5ms
A Comparison of the Histopathologic Features of Thyroid Carcinomas with NTRK Fusions to Those with Other Malignant Fusions. (PubMed, Hum Pathol)
Thyroid neoplasms with a malignancy associated gene fusion are likely to be diagnosed as subtype/variant of PTC. Patients whose thyroid lesions harbor NTRK fusions present with a PTC-FV that on presentation has more aggressive clinicopathologic findings and are likely to have earlier disease recurrence.
Journal
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • PPARG (Peroxisome Proliferator Activated Receptor Gamma) • PAX8 (Paired box 8)
6ms
Clinicopathological and molecular characteristics of NTRK-rearranged spindle cell neoplasms in the gastrointestinal tract (PubMed, Zhonghua Bing Li Xue Za Zhi)
It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STRN (Striatin) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
6ms
Rapid molecular profiling utilising minimal quantities of endobronchial ultrasound-guided aspirates for the detection of Epidermal Growth Factor Receptor, KRAS, ALK, ROS1, RET, NTRK and MET gene alterations from patients with non-small-cell lung carcinomas on the Biocartis Idylla™ platform. (PubMed, Cytopathology)
Real-time PCR utilising the Idylla™ platform is rapid, utilises minimal amounts of tissue and provides accurate results. We propose this is a useful ancillary method to utilise alongside next-generation sequencing (NGS) in cases of urgent clinical requirement or EBUS aspirates with inadequate quantities of tissue for NGS.
Journal • Endobronchial ultrasound
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
6ms
A Study to Evaluate Safety, Tolerability and Pharmacokinetic of ND-003 Tablets in Healthy Adults (clinicaltrials.gov)
P1, N=104, Enrolling by invitation, Shenzhen NewDEL Biotech, Co., Ltd | Not yet recruiting --> Enrolling by invitation
Enrollment open
6ms
Journal
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CD34 (CD34 molecule) • NTRK (Neurotrophic receptor tyrosine kinase)
6ms
Enrollment open
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Augtyro (repotrectinib)
6ms
Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib)
6ms
NTRK gene fusion testing and management in lung cancer. (PubMed, Cancer Treat Rev)
Larotrectinib and entrectinib are first-generation TRK inhibitors that have demonstrated efficacy in patients with TRK fusion lung cancers. Among these assays, RNA-based next-generation sequencing (NGS) can be considered a gold standard for detecting NTRK gene fusions; however, several alternatives with minimally acceptable sensitivity and specificity are also available in areas where widespread access to NGS is unfeasible. This review highlights the importance of testing for NTRK gene fusions in lung cancer, ideally using the gold-standard method of RNA-based NGS, the various assays that are available, and treatment algorithms for patients.
Review • Journal
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NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)