Aprea's WEE1 Inhibitor Achieves 50% Tumor Reduction, 87% CA-125 Decline at 220 mg
Aprea reported a second unconfirmed partial response in the Phase 1 ACESOT-1051 trial for APR-1051 at the 220 mg dose, with 50% tumor shrinkage and an 87% CA-125 reduction in a PPP2R1A-mutant endometrial cancer patient. The WEE1 inhibitor has induced Grade 1 adverse events across 22 patients dosed from 10 mg to 220 mg.
1. Clinical Response at 220 mg Dose
A patient with advanced endometrial cancer harboring a PPP2R1A mutation achieved an unconfirmed partial response at the 220 mg APR-1051 dose in the Phase 1 ACESOT-1051 trial, with target lesion measurements reduced by 50% and CA-125 biomarker levels falling 87% from 362 U/mL to 47 U/mL.
2. Preliminary Efficacy Across Cohorts
The trial has recorded two unconfirmed partial responses at first imaging assessments—at 150 mg and 220 mg—in endometrial cancer patients with PPP2R1A mutations, while five additional patients across 70 mg to 150 mg cohorts have shown stable disease, indicating preliminary anti-tumor activity in genomically defined solid tumors.
3. Safety and Tolerability
APR-1051 has demonstrated a favorable safety profile, with all 22 patients dosed from 10 mg to 220 mg experiencing no higher than Grade 1 treatment-emergent adverse events, supporting Aprea’s aim of differentiated WEE1 inhibition with an improved therapeutic index.
4. Trial Progress and Next Steps
Enrollment in the 220 mg cohort continues and will expand to include more PPP2R1A-mutant endometrial and HPV-positive head and neck cancer patients, with the company expecting further trial updates in the second quarter of 2026.