43P Updated efficacy and circulating tumour (ct)DNA analysis in patients (pts) with TRK fusion lung cancer treated with larotrectinib (laro)

NTRK gene fusions are oncogenic drivers in various cancers, including lung cancer. Laro is the first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for use in pts with tumours harbouring an NTRK gene fusion. We report efficacy and safety with ctDNA analysis in pts with TRK fusion lung cancer treated with laro. Pts treated with laro in two clinical trials (NCT02122913, NCT02576431) were analysed. NTRK gene fusions were determined by local testing before enrolment. Laro was administered at 100 mg twice daily. Response was assessed by an independent review committee (IRC) per RECIST v1.1. ctDNA was analysed using Guardant360 and GuardantOMNI. As of 20 July 2022, 30 pts (12 pts with CNS metastases) were enrolled. Pts received a median of two prior lines of systemic therapy, with 20 pts (67%) receiving two or more. Among 27 IRC-eligible pts, overall response rate was 74% (95% CI 54–89; three complete response CR, 17 partial response PR, four stable disease SD, two progressive disease PD and one not evaluable). Median duration of response was 33.9 months (95% CI 9.5–not estimable NE); median follow-up was 22.9 months. Median progression-free survival was 33.0 months (95% CI 11.3–NE); median follow-up was 24.7 months. Median overall survival was 39.3 months (95% CI 17.2–NE); median follow-up was 23.1 months. Treatment-related adverse events were mostly Grade 1/2. ctDNA data were available for 14 pts. ctDNA analysis detected NTRK gene fusions in six of the 14 pts at treatment start. Baseline mutations were identified in nine pts. Eleven pts had prior immunotherapy. Best response to prior immunotherapy was one CR, one SD, two PD, two not evaluable and five unknown. The best responses to laro in these 11 pts were eight PR, two SD, and one PD. Laro demonstrated durable responses, extended survival benefit and a favourable safety profile in pts with advanced lung cancer harbouring NTRK gene fusions. These results support the adoption of ctDNA next-generation sequencing panels that include NTRK gene fusions in clinical practice.