Background: The highly selective TRK inhibitor larotrectinib is approved for the treatment of adult and pediatric cancers that harbor NTRK gene fusions; it achieves a 79% overall response rate (ORR) in this population (Hong et al., Lancet Oncol, 2020). The activity of larotrectinib in adults alone was further characterized in this update with a larger series of patients and more mature durability data. Methods: Adults (aged ≥18 y) with TRK fusion cancer treated in three larotrectinib clinical trials (NCT02122913, NCT02576431, and NCT02637687) were analyzed. Larotrectinib was administered 100 mg BID until disease progression, withdrawal, or unacceptable toxicity. ORR was investigator-assessed (RECIST v1.1). Compared to previously presented data on 74 patients, this expanded data set includes an additional 42 patients (data cutoff: July 15, 2019). Results: 116 adults (median age: 56 y, range 19–84 y; 53% female) with TRK fusion cancer were treated. Tumor types included thyroid cancer (22%), salivary gland cancer (19%), soft tissue sarcoma (16%), lung cancer (12%), colon cancer (7%), melanoma (5%), breast cancer (5%), GIST (3%), and 9 other types (≤2% each). NTRK fusions involved NTRK1 (43%), NTRK2 (3%), and NTRK3 (54%). 78% of patients had received prior systemic therapy (with 68% of those receiving ≥2 prior therapies). The ORR was 71% (95% CI 62–79): 10% complete response, 60% partial response (2% pending confirmation), 16% stable disease, 9% progressive disease, 3% not determined. In patients with brain metastases, the ORR was 71% (95% CI 42–92; 10 of 14 patients, all partial responses). Median duration of response for the overall data set (n = 116) was 35.2 mo (95% CI 21.6–not estimable [NE]). Median progression-free survival was 25.8 mo (95% CI 15.2–NE). Median overall survival was not reached (range 0.5+ to 51.6+ mo) at a median follow-up of 15.8 mo. Duration of treatment ranged from 0.10 to 51.6+ mo. 12% of patients had dose reductions. One patient (1%) discontinued due to a larotrectinib-related adverse event (AE). AEs were mostly grade 1–2; no new unexpected AEs were reported. Conclusions: In an expanded data set of adults with TRK fusion cancer, larotrectinib demonstrated robust and durable tumor-agnostic efficacy and favorable safety, supporting NTRK gene fusion testing in patients with solid tumors of any type. Clinical trial information: NTC02122913, NCT02576431, NCT02637687.