Background: Pralsetinib is an investigational, highly potent, selective RET kinase inhibitor targeting oncogenic RET alterations. We provide the registrational dataset for pts with RET fusion+ NSCLC with and without prior treatment from the global ARROW study. Methods: ARROW (75 sites in 11 countries; NCT03037385) consists of a phase I dose escalation to establish recommended phase II dose (400 mg once daily [QD] orally) and phase II expansion cohorts defined by tumor type and/or RET alteration. Primary objectives were overall response rate (ORR; blinded independent central review per RECIST v1.1) and safety. Efficacy analyses are shown for response-evaluable pts (REP) with RET fusion+ NSCLC who initiated 400 mg QD pralsetinib by July 11 2019 and safety for all pts (regardless of diagnosis) treated with 400 mg QD. Results: As of November 18 2019, 354 pts with advanced solid tumors had received pralsetinib at starting dose of 400 mg QD with median follow-up 8.8 months. ORR, disease control rate (DCR), and % of pts with tumor size reduction are shown in the table for pts with metastatic RET fusion+ NSCLC (n=116; 72% KIF5B; 16% CCDC6; 12% other/fusion present but type unknown) and with prior platinum treatment (n=80) or without prior systemic treatment (n=26). ORR was similar regardless of RET fusion partner, prior therapies, or central nervous system involvement. Overall there were 7 (6%) complete responses, 4 (5%) in prior platinum pts and 3 (12%) in treatment naïve pts; median time to response overall was 1.8 months and median duration of response (DOR) was not reached (95% CI, 11.3–NR). In the safety population (n=354), most treatment-related adverse events (TRAEs) were grade 1-2, and included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%) and hypertension (20%). 4% of pts in the safety population (all tumor types) discontinued due to TRAEs. Conclusions: Updated, registrational, centrally reviewed data demonstrate that pralsetinib has rapid, potent, and durable clinical activity in pts with advanced RET fusion+ NSCLC regardless of RET fusion genotype or prior therapies, and QD oral dosing is well-tolerated. Clinical trial information: NCT03037385.

^aIncluding n=10 with prior non-platinum treatment

^bIncluding n=2 with partial response pending confirmation