604TiP ON-TRK: A non-interventional study of larotrectinib in patients with TRK fusion cancer

Abstract

NTRK gene fusions are rare oncogenic drivers in a range of tumour types. The CNS-active and highly selective EMA- and FDA-approved TRK inhibitor, larotrectinib, demonstrated an objective response rate (ORR) of 79% and a median duration of response (DoR) of 35.2 mos in a pooled analysis of 159 adult and paediatric patients (pts) with TRK fusion cancer (Hong et al. Lancet Oncol 2020). A low incidence of Grade 3-4 adverse events (AEs) was reported. Due to the rarity of TRK fusion cancer and relatively small number of patients treated to date, real-world efficacy and long-term safety data with larotrectinib in a larger population are needed. The ON-TRK study is a global, prospective, multi-cohort, non-interventional study. Pts with locally advanced or metastatic solid tumours with demonstrated NTRK gene fusions and scheduled to receive larotrectinib are eligible. Exclusion criteria include prior TRK inhibitor therapy or presence of NTRK genomic alterations other than fusions. Paediatric pts (<18 yrs) will comprise one cohort. Adults will be enrolled into cohorts based on tumour type: gastrointestinal, head and neck, lung, melanoma, primary CNS, soft tissue sarcoma, or other. NTRK gene fusions will be detected locally by next-generation sequencing, fluorescence in situ hybridisation, reverse-transcription polymerase chain reaction, or any other genomic tests able to detect NTRK gene fusions. Dose and duration of treatment will be at the investigator’s discretion, based on product information. Paediatric pts will be followed for ≥5 yrs unless lost to follow-up, withdrawal, or death. Pts in all other cohorts will be followed for ≥2 yrs unless lost to follow-up, withdrawal, or death. The primary endpoint is safety. Secondary endpoints are efficacy (ORR, disease control rate, DoR, time to response, PFS, and OS) by investigator assessment; treatment patterns; efficacy in subgroups (including by age, NTRK gene, fusion partner, testing method, country/region, and prior therapy); and long-term effects of larotrectinib on growth, neurologic outcomes, developmental milestones, and sexual development in paediatric pts. Target accrual is 300 pts including ≥30 paediatric pts. NCT04142437: First posted 29 October 2019. Editorial assistance was provided by Michael Sheldon and Annabel Ola (Scion, London, UK), funded by Bayer HealthCare Pharmaceuticals, Inc. Bayer HealthCare Pharmaceuticals, Inc.