Patient With Head and Neck Cancer Dosed in Trial of APR-1051

A patient with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) has been dosed in ACESOT-1051, a phase 1 clinical trial evaluating APR-1051 in advanced solid tumors with cancer-associated gene alterations.

The development was announced in a news release from clinical-stage biopharmaceutical company Aprea Therapeutics, Inc.

APR-1051, according to the National Cancer Institute, is an oral inhibitor of the WEE1 protein kinase. Overexpression of WEE1 occurs in several different cancer types, with a high expression of WEE1 associated with poor outcomes. APR-1051 treatment is intended, by inhibiting WEE1, to promote premature cell division and prolonged blocking of the cell cycle, resulting in an accumulation of unrepaired DNA damage and leading to the death of susceptible tumor cells.

The patient with HPV-positive HNSCC was the first patient to be dosed in Cohort 5 of ACESOT-1051, receiving 70 milligrams once daily of APR-1051, according to the news release. Open-label data from the study are expected to be released in the second half of 2025, Aprea reported.

HPV-positive cancers, according to the news release, are among those potentially susceptible to WEE1 inhibition, and approximately 70% of the 20,000 cases oropharyngeal squamous cell carcinoma, or HNSCC that occurs in the oropharynx, diagnosed each year in the United States are attributable to HPV.

The ACESOT-1051 trial, evaluating APR-1051 monotherapy among patients with advanced solid tumors, is currently recruiting, with an anticipated eventual enrollment of 79 patients, according to its listing on clinicaltrials.gov. The trial is being held at three locations in Texas, including The University of Texas MD Anderson Cancer Center in Houston, NEXT Oncology – Dallas in Irving and NEXT Oncology – San Antonio. The trial has an estimated primary completion date of June 2027, and an estimated study completion date of June 2028, according to the listing.

“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 Dr. Philippe Pultar, 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.”

Cancers known as head and neck cancers, according to the National Cancer Institute, usually begin the squamous cells lining the mucosal surfaces of the head and neck, such as inside the mouth, the throat and the voice box, and are referred to as squamous cell carcinomas of the head and neck.

ACESOT-1051 has been designed to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary effectiveness of APR-1051. The drug will be administered once a day for 28-day cycles. Part 1 of the study will be a dose-escalation phase, expected to enroll up to 39 patients, with Part 2 with up to 40 patients being designed for dose optimization with the goal of selecting a recommended phase 2 dose, according to the news release, which stated that the study will eventually be performed at up to 10 sites across the United States.

For more information on the trial, use the trial ID, NCT06260514, at clinicaltrials.com.

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