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

NCT07578467 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 859861
• Study Type: interventional
• Target: 35
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma; HPV (Human Papillomavirus)-Associated Carcinoma; HPV Associated Cancers; Oropharyngeal HPV Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase Ib: Feasibility of a neo-adjuvant approach combining ATRN with SBRT before TORS

  This will be judged by whether patients are able to have their planned surgery within 6 weeks after the study treatment, and whether there are no problems during surgery that the study doctor believes were caused by the study treatment.

  Within 6 weeks after study treatment

• Phase II: Major pathologic response (MPR) rate of radiated nodal disease

  Researchers will measure how many patients have a strong treatment response in the affected lymph nodes that were treated with radiation, based on what is seen when the tissue is examined.

  Immediately after standard of care primary tumor removal surgery

Secondary Outcomes (5)

• Phase II: To assess safety of ATR inhibitor ATRN-119 with nodal SBRT prior to surgery

  From start of study treatment through standard of care 2-year Follow-Up visit

• Phase II: Radiographic response rates

  Pre-treatment MRI will be taken prior to enrollment as part of standard of care. Post-treatment Research MRI will be completed 1 week before standard of care tumor removal surgery.

• Phase II: Type of adjuvant treatment required

  Within 4 months of primary tumor removal surgery

• Phase II: Pathologic response of primary tumor and nodal disease

  Immediately after primary tumor removal surgery

• Phase II: Assessment of Patient Reported quality of life

  From enrollment to 24 Month Follow-Up Visit

Other Outcomes (2)

• Phase II: Relapse-free survival (RFS) at two years

  From the completion of treatment, either surgery in those not receiving adjuvant therapy, or completion of all adjuvant therapy and will last for 2 years

• Phase II: Measures of activation of anti-tumor immunity in primary tumor and blood

  From enrollment to date of primary tumor removal surgery

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients will take 800mg of ATRN-119 every day for 10 days. On day 3 of dosing, they will return to clinic for 1 fraction of SBRT.

Drug: ATRN-119; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Interventions

ATRN-119 DRUG

ATRN-119 at 800 mg QD (every day) for 10 days

Treatment Arm

Stereotactic Body Radiation Therapy (SBRT) RADIATION

10 Gy administered to nodal disease (neck) only on day 3 of ATRN-119 dosing

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Patients that have been diagnosed with HPV-positive throat cancer (OPSCC) at an early stage (stage I or II), confirmed by a biopsy.
• Patients' blood calcium level is within a safe range
• Patients' blood, kidney, and liver health are strong enough, shown through specific medical test results
• If a participant is female, she must not be pregnant or breastfeeding.
• If a participant is male, he must agree to use highly effective birth control from the start of the study until a short period after the last dose of the study drug.

You may not qualify if:

• Patients with late-stage tumors (Stage III or IV)
• If the cancer has already spread to distant parts of the body (M1) when first diagnosed
• Prior advanced head and neck cancer requiring radiation or major surgery
• Patients whose original tumor site cannot be identified
• Patients that have a known additional malignancy that is progressing or requires active treatment
• Patients that had a surgical procedure performed within 7 days prior to first scheduled dose of ATRN-119. This does not include procedures that are used to diagnose or determine extent of study disease (such as biopsies).
• Patients taking medications that strongly affect how the body processes certain drugs (CYP enzymes) at the same time as the study treatment.
• Patients with active infections and/or receiving systemic antibiotics or anti-viral medications.
• Patients with uncontrolled HIV or active hepatitis B or C are usually not eligible. However, those whose infections are well-controlled on treatment for at least a month and meet certain viral load limits can participate
• Current or past diagnosis of leukemia within the past 5 years.
• Patients with a history of non-malignant gastrointestinal (GI) bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months.
• Patient has uncontrolled hypertension at time of enrollment.
• Patients who recently had serious kidney problems or kidney disease.
• Patients cannot have taken another experimental drug within 30 days-or within a period equal to five times that drug's half-life-before starting this study
• Medical illness that, in the opinion of the Investigator, may impact the safety of the patient

Sponsors & Collaborators

• John Lukens: lead
• Aprea Therapeutics: collaborator

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Papillomavirus Infections

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Nick Lukens, MD

CONTACT

215-662-6567; RadOncCRU@PennMedicine.upenn.edu

Casey Hanna

CONTACT

215 - 615 - 1611; casey.hanna@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: May 11, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): May 31, 2030
• Study Completion (Estimated): May 31, 2030
• Last Updated: May 11, 2026

Record last verified: 2026-04