Efficacy and safety of pralsetinib as first-line treatment of RET fusion–positive advanced or metastatic non–small cell lung cancer (NSCLC): The phase 3 AcceleRET-Lung study.

8504 Background: Pralsetinib, an oral tyrosine kinase inhibitor, selectively and potently targets oncogenic RET fusion and mutation proteins. Pralsetinib is FDA approved to treat adults with metastatic RET -altered NSCLC. We present efficacy and safety of pralsetinib vs standard of care (SOC) in first-line RET fusion-positive NSCLC from a randomized phase 3, open-label study, AcceleRET-Lung (NCT04222972). Methods: AcceleRET-Lung was conducted at 74 sites in 22 countries. Adults with RET fusion-positive advanced or metastatic NSCLC received pralsetinib 400 mg/d or platinum-based SOC therapy. Crossover to pralsetinib was optional upon progression. The primary end point was progression-free survival (PFS) per RECIST v1.1. Secondary end points included overall response rate (ORR), overall survival (OS), duration of response (DOR), and safety. Efficacy was evaluated in randomized patients (intent-to-treat population [ITT]). Safety was assessed in patients receiving ≥1 dose of study drug. Results: 223 ITT patients were randomized to pralsetinib (n=110) or SOC (n=113). Pralsetinib and SOC groups had similar baseline characteristics (median age: 62 and 63 y, respectively; female: 48% and 57%; median lesions: both 4; brain metastases: 15% and 16%). The study was terminated early per sponsor decision on January 27, 2025. ITT patients in the pralsetinib group had significantly greater median PFS vs SOC (18.7 vs 9.0 mo; P =0.003), ORR (65.5% vs 41.6%; P