OBJECTIVES: NTRK gene fusions are rare oncogenic drivers, occurring in only approximately 0.30% of solid tumors, for which there are currently 2 approved therapies based on single-arm trials. Finding real world data (RWD) that are suitable for comparison is challenging, due to the absence of genomic information in traditional RWD data sources and the rarity of patients with NTRK gene fusion-positive (NTRK+) tumors seen by clinical sites. We explored an innovative, multi-faceted approach to build a real-world dataset of patients with NTRK+ solid tumors.

METHODS: Two approaches were taken to identify NTRK+ patients: 1) identification and evaluation of existing clinicogenomic data sources, and 2) surveying global clinical sites. Clinicogenomic data sources were evaluated based on pre-defined attributes to assess fit-for-purpose. A global clinical site survey was also conducted across sites that screened for or were involved in the TRK inhibitor clinical trial program or were identified through a systemic literature review.

RESULTS: Three clinicogenomic data sources were eligible; 19 were excluded due to incomplete clinical data, inaccessible patient-level data, or inability to validate NTRK fusion status. The global clinical site survey included 915 sites from 25 countries. Despite multiple outreach efforts, 47 (5.1%) sites responded, and 7 (0.8%) sites were considered eligible. Site challenges included: unresponsiveness, contracting delays, site-specific requirements, data entry delays, regulatory authority/ethics committee submissions, and site staff turnover. Average time for site activation was approximately 250 days. A comparative study is underway utilizing this clinicogenomic and site-based data approach (NCT05192642), with 75 NTRK+ real-world patients meeting eligibility criteria thus far.

CONCLUSIONS: The rarity of NTRK+ patients present challenges for identification of sufficient and robust RWD sources that can be used in a comparative way to benchmark results against single-arm trials. This novel approach provides a solution to identify fit-for-purpose RWD for patients with rare cancers.