On March 31, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported that a patient with HPV+ head and neck squamous cell carcinoma (HNSCC) has been dosed in the ongoing ACESOT-1051 clinical trial evaluating APR-1051 (Press release, Aprea, MAR 31, 2025, View Source [SID1234651658]). This is the first patient to be dosed in Cohort 5 (70 mg once daily) of the study. Open label data from the study are expected in the second half of 2025.

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WEE1 inhibition has emerged as a promising strategy for targeting tumor cells with high replication stress and DNA damage accumulation. HPV driven cancers, including HPV+ HNSCC, are characterized by defects in the DDR pathway, making them potentially susceptible to WEE1 inhibition. HPV+ cancers are those where the underlying cause is persistent infection with human papillomavirus, a group of viruses that infect the skin and mucous membranes. A high proportion of HNSCC cases are attributable to HPV. An estimated 70% of the 20,000 cases of oropharyngeal squamous cell carcinoma (HNSCC that occurs in the oropharynx) seen annually in the US are attributable to HPV.

APR-1051 is a potent and selective small molecule that has been designed to potentially solve tolerability challenges of the WEE1 class. The ongoing ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) clinical trial is a Phase 1 trial evaluating single-agent APR-1051 in patients with advanced solid tumors harboring cancer-associated specific gene alterations.

"Enrollment of the first patient with HPV+ head and neck cancer in the Phase 1 ACESOT-1051 trial is an important step and is in line with our goal of identifying patient populations most likely to benefit from WEE1 inhibition," said Philippe Pultar MD., Senior Medical Advisor and Lead WEE1 Clinical Development of Aprea. "We are pleased with the progress of the trial and encouraged by the safety profile of APR-1051 to date. We look forward to continuing the study as we work toward identifying the optimal dose for future studies. We continue to believe that APR-1051 has best in class potential."

The latest patient in ACESOT-1051 was enrolled at MD Anderson Cancer Center. Aprea recently entered into a Material Transfer Agreement (MTA) with MD Anderson to support preclinical research aimed at exploring the potential of APR-1051 in treating HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) expressing genomic markers of replication stress.

ACESOT-1051 Study Design

ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts. Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels (10mg, 20mg and 30mg) used accelerated titration. Bayesian Optimal Interval (BOIN) design is now being employed for the remaining dose levels (50mg and above). Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D).

The primary objectives of the study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and RP2D; secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective. The University of Texas MD Anderson Cancer Center is the lead site, and the study will be performed at between 3 and 10 sites in the U.S. For more information refer to clinicaltrials.gov NCT06260514.