Background: RET fusions are targetable oncogenic drivers in 1–2% of non-small cell lung cancer (NSCLC). ARROW (NCT03037385) supported the US FDA approval of pralsetinib, a highly potent oral selective RET inhibitor for RET-altered NSCLC and thyroid cancer. Here, we present updated results for a larger population of patients with RET fusion–positive NSCLC enrolled in ARROW. Methods: ARROW is a phase 1/2 open-label study conducted at 84 sites in 13 countries. Phase 2 expansion cohorts included patients with RET fusion–positive NSCLC. Initially, all treatment-naïve patients were not candidates for platinum-based therapy, a requirement removed by protocol amendment in July 2019. Primary objectives are overall response rate (ORR; blinded independent central review [BICR] per RECIST v1.1), assessed for patients with baseline measurable disease, and safety. Results: Updated analyses were completed as of Nov 6, 2020 (data cut-off), for patients who initiated pralsetinib 400 mg QD by May 22, 2020 (enrollment cut-off). Efficacy results, including analyses for treatment-naïve patients enrolled after eligibility criteria were revised to allow candidates for platinum-based therapy, are shown in the Table. Conclusions: Pralsetinib showed rapid, potent, and durable clinical activity in patients with RET fusion-positive NSCLC (regardless of prior therapies), including poor prognosis patients not eligible for platinum-based therapy. Overall, pralsetinib was well-tolerated. These data highlight the need for RET testing early in the course of disease to identify candidates who may benefit from treatment with pralsetinib.Clinical trial information: NCT03037385

CI, confidence interval; mo, months; NE, not estimable; NR, not reached; PFS, progression-free survival. ^aMeasurable disease population. ^bConfirmed response or stable disease of ≥16 weeks. ^cAssessed in full efficacy population. ^dn = 136. ^en = 75. ^fn = 28. ^gMedian follow-up for PFS in this population was 8.2 mo. In all patients enrolled in ARROW who received pralsetinib 400 mg QD by May 22, 2020 irrespective of tumor type (n = 471; data cut-off Nov 6, 2020), the most common (≥25%) treatment-related adverse events (TRAEs) were increased aspartate aminotransferase (39%), anemia (35%), increased alanine aminotransferase (27%), constipation (26%) and hypertension (25%). Overall, 6% of patients discontinued treatment due to TRAEs.