%0 Clinical Trial, Phase I
%T PRT543, a protein arginine methyltransferase 5 inhibitor, in patients with advanced adenoid cystic carcinoma: An open-label, phase I dose-expansion study.
%A Ferrarotto R
%A Swiecicki PL
%A Zandberg DP
%A Baiocchi RA
%A Wesolowski R
%A Rodriguez CP
%A McKean M
%A Kang H
%A Monga V
%A Nath R
%A Palmisiano N
%A Babbar N
%A Sun W
%A Hanna GJ
%J Oral Oncol
%V 149
%N 0
%D 2024 Feb 19
%M 38118249
%F 5.972
%R 10.1016/j.oraloncology.2023.106634
%X <B>OBJECTIVE: </B>Currently, no systemic treatments are approved for patients with recurrent and/or metastatic (R/M) adenoid cystic carcinoma (ACC). PRT543, a protein arginine methyltransferase 5 inhibitor that downregulates NOTCH1 and MYB signalling in tumours, is a potential candidate for R/M ACC treatment. We report the safety, tolerability and preliminary efficacy of PRT543 in a dose-expansion cohort of patients with R/M ACC.<BR><B>METHODS: </B>This phase I multicentre, open-label, sequential-cohort, dose-escalation and dose-expansion study (NCT03886831) enrolled patients with advanced solid tumours and select haematologic malignancies. Dose-escalation study design and results were reported previously. In the dose expansion, patients with R/M ACC received recommended phase II doses of 35 or 45 mg PRT543 orally on days 1-5 of each week. Primary objectives were to establish the safety and tolerability of PRT543. Secondary objectives included efficacy.<BR><B>RESULTS: </B>Between February 2019 and May 2022, 56 patients with ACC were enrolled across 23 US sites and received either 35 mg (n = 28) or 45 mg (n = 28) of PRT543. Overall, 23% of patients experienced a grade 3 treatment-related adverse event, most commonly anaemia (16%) and thrombocytopaenia (9%). No grade 4/5 treatment-emergent adverse events were reported. Median progression-free survival was 5.9 months (95% CI: 3.8-8.3). The clinical benefit rate was 57% (95% CI: 43-70). Overall response rate (per Response Evaluation Criteria in Solid Tumours v1.1) was 2%, with 70% of patients having stable disease.<BR><B>CONCLUSIONS: </B>In this analysis, PRT543 was tolerable, and the observed efficacy was limited in patients with R/M ACC.