Combining Neo-adjuvant ATR-inhibition With Nodal SBRT for Early-stage Resectable HPV+ OPSCCs

This research study is testing whether a new study drug (called ATRN-119) is safe and effective when combined with a single, highly targeted dose of radiation therapy (called stereotactic body radiation therapy or SBRT) to treat early-stage throat cancer that is caused by HPV. The goal of this study is to treat cancer effectively while reducing side effects and helping patients maintain a better quality of life over the long term. Researchers hope that this approach will be just as successful-or possibly more successful-than current treatments, which already have high cure rates. Participants will: * Take 800mg of ATRN-119 every day for 10 days * Receive 1 treatment (called a "fraction") of SBRT to the neck on day 3 of ATRN-119 dosing. * Keep a short diary to track ATRN-119 dosing. The diary will be provided by study team * Receive standard of care treatment after treatment with ATRN-119 + SBRT including TransOral Robotic Surgery (TORS) to remove the primary tumor with Neck Dissection and adjuvant therapy (if indicated) * Receive additional safety checkups and tests by researchers during routine visits with their cancer doctor for 2 years after study treatment

NCT Number	NCT07578467
Lead Sponsor	Abramson Cancer Center at Penn Medicine Collaborators: Aprea Therapeutics
Conditions	HPV Positive Oropharyngeal Squamous Cell Carcinoma, Squamous Cell Carcinoma, HPV (Human Papillomavirus)-Associated Carcinoma, HPV Associated Cancers, Oropharyngeal HPV Squamous Cell Carcinoma
Enrollment	35 participants
Start Date	2026-08-31
Primary Completion	2030-05-31 (estimated)
Study Completion	2030-08-31 (estimated)
Updated on ClinicalTrials.gov	2026-07-08