(P 550) ON-TRK: A NON-INTERVENTIONAL STUDY OF LAROTRECTINIB IN PATIENTS WITH TRK FUSION SOLID TUMORS

Objective: Increasingly, both the health authorities and medical community are investing time and resources into evaluating real-world data on the efficacy and safety of precision biomarker-based treatments. Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various cancers. Larotrectinib is a first-in-class, highly selective, central-nervous-system-active tropomyosin receptor kinase (TRK) inhibitor, approved for tumor-agnostic use in pediatrics and adults with TRK fusion cancer. Enrolling patients to the ON-TRK study (NCT04142437), a Food and Drug Administration and European Medicines Agency post-marketing requirement for the approval of larotrectinib, is critical to continue to gain real-world knowledge about the treatment of patients with TRK fusion cancer and will contribute to the broader understanding of personalized cancer care. Here, we describe the ON-TRK clinical trial, which is currently in progress in patients with TRK fusion cancer.

Methods: ON-TRK is a non-interventional, open-label, global, prospective, multi-cohort study enrolling adult (aged ≥18 years) and pediatric (from birth to 18 years) patients with TRK fusion, locally advanced or metastatic solid tumors scheduled to receive larotrectinib (Figure 1). Patients with cancer harboring NTRK gene fusions, detected locally, are eligible. Patients who have had prior TRK inhibitor therapy and patients with NTRK genomic alterations other than fusions are excluded. Decisions on the dose and duration of treatment are at the discretion of the treating physician. The study objectives and variables are listed in Table 1. The primary endpoint is safety, including specific long-term safety parameters in pediatric patients. Secondary endpoints include efficacy (objective response rate, disease control rate, time to response, duration of response, progression-free survival, and overall survival), efficacy in subgroups (including age, NTRK gene and fusion partner, testing method, country/region, and prior therapy), long-term effects of larotrectinib in pediatric patients, and dosing patterns.

The effects of larotrectinib on growth and developmental milestones in pediatric patients will be reported, including change in height and weight from baseline, age at adrenarche for males and menarche for females, number and percentage of patients with abnormal Tanner stages, and abnormal neurological assessments. All variables will be analyzed using descriptive statistics.

Pediatric and adult patients will be followed for ≥5 years and ≥2 years, respectively, unless lost to follow-up, withdrawal, or death. Enrollment is ongoing worldwide and will include up to 300 patients, with ≥30 pediatric patients. As of May 2023, 70 patients have been enrolled, including 13 patients with either infantile fibrosarcoma or soft tissue sarcoma.

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