NTRK1 fusion

In conclusion, EBC samples provide a valuable, noninvasive medium for detecting clinically relevant and previously uncharacterized fusion transcripts in non-small cell lung cancer (NSCLC). The high concordance between EBC and tissue biopsies suggests that EBC could complement tissue biopsy for effective diagnosis and monitoring of NSCLC. These findings underscore the importance of comprehensive molecular profiling using multiple sample types to enhance diagnostic precision and optimize therapeutic outcomes in lung cancer management.

P1, N=82, Recruiting, VM Oncology, LLC | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jul 2026

After receiving dacomitinib and almonertinib sequentially, plasma-based NGS revealed the emergence of EGFR T790M-trans-C797S mutations, prompting a switch to a combination therapy of almonertinib and gefitinib...Larotrectinib was incorporated into the dual EGFR-TKI regimen, forming a triplet therapy...This is the first reported case of a novel, targetable POT1::NTRK3 fusion as a potential off-target mechanism mediating EGFR-TKI resistance, occurring alongside MET amplification in a patient with NSCLC harboring acquired EGFR L858R/T790M/C797S mutations. Concomitant inhibition of EGFR, NTRK, and MET was safe and resulted in a significant response, underscoring the importance of precision medicine guided by matched NGS.

Surgical resection is the mainstay of treatment for most patients. Distinguishing these tumors from morphologic mimics is significant because patients with advanced-stage disease may be treated with TRK inhibitors.

There was little overlap between the genes involved as 5'-partners (31 different genes) and 3'-partners (37 different genes). This study shows the clinical utility of a next-generation sequencing gene fusion detection assay for the diagnosis and treatment of sarcomas.

Unlike its efficacy in NTRK-fusion positive cancers, larotrectinib did not demonstrate a signal of efficacy among tumors with NTRK overexpression.

The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

Since BRAF activation occurs in BRAF fusion gene tumors and BRAF mutations, they could share a similar mechanism in tumorigenesis. This case suggests the further expansion of kinase-related spindle cell tumors.

P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026

We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (KIF5B)-NTRK1 gene fusion that responds well to entrectinib...Moreover, in vitro experiments showed that the fusion gene could exert oncogenic properties by activating the MAPK and PI3K/AKT signaling pathways. To summarize, our findings broaden the spectrum of NTRK gene fusions in the context of lung adenocarcinoma.

P2, N=31, Active, not recruiting, Children's Oncology Group | N=70 --> 31

Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.