1654P Updated ARROW data: Pralsetinib in patients (pts) with advanced or metastatic RET-altered thyroid cancer (TC)

Oncogenic RET alterations are targetable markers in pts with TC. In the phase I/II ARROW trial (NCT03037385; data cutoff 12 Apr 2021; intention-to-treat [ITT] population), pralsetinib at 400 mg once daily (QD) induced overall response rates (ORR) of 51% RET-mutant medullary TC (RETm MTC) previously treated cabozantinib and/or vandetanib (C/V), 72% treatment-naïve RETm MTC, and 86% fusion-positive (RET-fp TC). We report updated longer follow-up. Adult advanced or metastatic RET-altered from who initiated QD were included. Phase II primary endpoints: ORR by blinded independent central review (RECIST v1.1); safety. Key secondary duration (DoR); progression-free survival (PFS); (OS). Efficacy endpoints assessed ITT population (enrolment 18 Feb 2021); safety was all QD. At (18 Oct 2021), included 145 MTC (prior C/V: n=67; other prior systemic therapy: n=11; treatment naïve: n=67), 25 RET-fp Pts C/V had an 52% (35/67; 95% CI 39.7–64.6; 2 complete responses [CR]; 33 partial [PR]), a median DoR 25.8 months (95% 18.0–not estimable [NE]) PFS 19.7–35.0). Treatment-naïve (48/67; 59.3–82.0; 4 CR; 44 PR); not reached (NR). 84% (21/25; 63.9–95.5; 17 23.6 15.1–NE) 25.4 17.0–NE). these three cohorts, OS NR. (N=175), 29 (17%) experienced serious treatment-related adverse events (TRAE). One (0.6%) TRAE-related death (pneumocystis jirovecii pneumonia) reported. TRAEs led to discontinuation dose reduction 6% 53% pts, respectively. this analysis (ITT continued show efficacy acceptable profile