Knockdown of NTRK1, which encodes TrkA, reduced cell viability and sensitized ATC cells to paclitaxel. Entrectinib was well tolerated at the administered dose, with no significant changes in body weight and serum biochemical markers. Collectively, these findings identify TrkA as a potential therapeutic target in ATC and support further investigation of entrectinib-based combination strategies to improve ATC treatment outcomes.

These findings in rat models and in silico docking indicate that nicardipine increases entrectinib exposure. While these results underscore the risk of significant DDIs, further clinical studies in humans are required to confirm this interaction and determine if entrectinib dose adjustments are necessary to mitigate adverse events.

P2, N=534, Active, not recruiting, Hoffmann-La Roche | Trial completion date: May 2026 --> Jun 2027 | Trial primary completion date: May 2026 --> Jun 2027

No statistically significant difference was observed (P=0.65). This study did not find evidence that baseline PD-L1 expression significantly influences the efficacy of entrectinib in advanced ROS1-rearranged NSCLC patients.

P3, N=68, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Dec 2026 --> Jun 2030

Entrectinib was administered, and an excellent response was observed. This case emphasizes the relevance of performing NGS in cases with unusual clinicopathological findings to identify potential treatment options. Importantly, the morphology deviated from the classic fibrosarcoma-like appearance described in most adult NTRK3-fused neoplasms and broadens the morphological spectrum in which these neoplasms should be considered.

Targeted therapies with TRK inhibitors (TRKi), including larotrectinib and entrectinib, have shown promising efficacy with rapid and durable responses for patients with LGGs and HGGs. Overall, TRKi represent a significant advance for treating NTRK fusion-positive CNS tumors, especially in pediatric populations, offering new hope for patients with limited treatment options. Further studies are required to optimize their use and address unresolved challenges.

P1, N=13, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026

NTRK gene fusions are a critical marker for pediatric soft tissue tumors and are used for precision medicine in these tumors. NTRK gene fusions are used as diagnostic markers for infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and they play a critical role in the management of these tumors.

Combination therapy with osimertinib and entrectinib induced regression of pulmonary lesions, but the patient ultimately discontinued all targeted agents due to the development of severe hepatorenal failure and Escherichia coli-associated sepsis. This case highlights the need for additional research into the safety profile of EGFR-TKI/NTRK inhibitor combination regimens in resistant NSCLC.

Notably, Entrectinib ameliorated LPS-induced memory impairments in vivo. Collectively, these findings indicate that Entrectinib attenuates neuroinflammation and improves memory performance, supporting its potential therapeutic relevance for neuroinflammation-associated cognitive disorders.