Aprea Therapeutics Announces Additional Positive Clinical Activity for WEE1 Inhibitor, APR-1051, Including Second Partial Response in Ongoing ACESOT-1051 Trial

Core Viewpoint - Aprea Therapeutics announced preliminary data from the Phase 1 ACESOT-1051 trial for its WEE1 kinase inhibitor APR-1051, showing promising anti-tumor activity in patients with advanced endometrial cancer, particularly those with PPP2R1A mutations [1][5]. Trial Findings - The trial has reported a second unconfirmed partial response in a patient with advanced endometrial cancer at the 220 mg dose level, with a 50% reduction in target lesion measurements and a significant drop in the tumor biomarker CA-125 from 362 U/mL to 47 U/mL, representing an 87% decrease [2][3]. - The trial has treated a total of 22 patients at doses ranging from 10 mg to 220 mg, with the ongoing evaluation of safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity [6][10]. - Two patients with endometrial cancer harboring PPP2R1A mutations achieved unconfirmed partial responses at their first scan, observed at the 150 mg and 220 mg dose levels [8]. Safety and Tolerability - The treatment has been well tolerated, with only Grade 1 treatment-emergent adverse effects reported in the responding patient [3][7][14]. - The good safety profile supports the development strategy of differentiated WEE1 inhibition, aiming for an improved therapeutic index [5][7]. Future Directions - The company plans to expand enrollment in the 220 mg dose cohort, particularly focusing on patients with PPP2R1A endometrial and HPV-positive head and neck squamous cell carcinoma [9]. - Further updates from the trial are expected in the second quarter of 2026, reinforcing the ongoing commitment to advancing APR-1051 [4][10].