Ctni-75. efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (trk) fusion primary central nervous system (cns) tumors: an updated analysis

Abstract BACKGROUND Larotrectinib is a highly selective TRK inhibitor approved for tumor-agnostic use in patients with various tumor types, including primary CNS tumors. Here, we report the independent central review and updated data on patients with TRK fusion-positive primary CNS tumors. METHODS Patients with TRK fusion primary CNS tumors enrolled in two clinical trials (NCT02637687, NCT02576431) were included. Responses were independent review committee (IRC)-assessed. RESULTS As of July 2022, 41 patients were eligible for response assessment by IRC. The median age at enrollment was 11 years (range 1-79). Tumor histologic groups included: high-grade glioma (HGG; n=25), low-grade glioma (LGG; n=9), and other (n=7). Sixteen (39%) patients had received ≥ 2 prior systemic therapies. For all patients, objective response rate (ORR) was 22% (95% CI 11–38): one complete response, eight partial response, 20 stable disease, and 12 progressive disease. For pediatric patients (n=28), the ORR was 29% (95% CI 13–49). For pediatric patients with HGG and LGG, ORRs were 14% (95% CI 2–43) and 57% (95% CI 18–90), respectively. The disease control rates at 24 weeks were 54% (95% CI 37–69) and 71% (95% CI 51–87) for all patients and pediatric patients, respectively. Medians for time to response, duration of response, progression-free survival, and overall survival (OS) were 1.9 months, 12.2 months (95% CI 3.7–not estimable), 11.1 months (95% CI 3.6–19.8), and not reached, respectively. The 48-month OS rate was 52%. Treatment duration ranged from 1 to 50+ months. Treatment-related adverse events (TRAEs) were mostly Grade 1/2. No patients discontinued treatment due to TRAEs. CONCLUSION Larotrectinib demonstrated rapid, durable responses and a manageable safety profile in patients with TRK fusion primary CNS tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing patients with CNS tumors.