Immunotherapy and Nodal-Sparing Irradiation for T-Cell Induction and Unmasking of Tumor Antigenicity in the Microenvironment for Head and Neck Cancer

NCT07773987 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: PRO00059024
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-comparative randomized Phase 2 study using the INITIUM regimen with or without elective nodal irradiation (ENI) delivered before surgery for resectable head and neck squamous cell carcinoma (HNSCC).

Conditions

Head and Neck Cancer Squamous Cell Carcinoma

Keywords

elective nodal irradiation; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (pCR) rate to INITIUM-HN with and without ENI.

  pCR is defined as no viable tumor in primary tumor or lymph nodes on pathological examination.

  Up to 10 weeks post-radiation therapy

Study Arms (2)

INITIUM regimen using ENI

EXPERIMENTAL

The INITIUM regimen includes two cycles of induction therapy with pembrolizumab, followed by pre-operative hypofractionated radiation (7 Gy × 5 fractions) and two additional cycles of pembrolizumab. Patients will receive ENI to non-clinically and radiographically involved draining nodal basins.

Drug: Pembrolizumab; Radiation: Radiotherapy; Radiation: ENI; Procedure: Surgery

INITIUM regimen without ENI

EXPERIMENTAL

The INITIUM regimen includes two cycles of induction therapy with pembrolizumab, followed by pre-operative hypofractionated radiation (7 Gy × 5 fractions) and two additional cycles of pembrolizumab. Patients will NOT receive ENI to non-clinically and radiographically involved draining nodal basins.

Drug: Pembrolizumab; Radiation: Radiotherapy; Procedure: Surgery

Interventions

Pembrolizumab DRUG

All patients will undergo induction with pembrolizumab (200 mg) given intravenously every three weeks for two cycles prior to radiation and two cycles after radiation.

Also known as: Keytruda

INITIUM regimen using ENI; INITIUM regimen without ENI

Radiotherapy RADIATION

All patients will receive 7 Gy daily for 5 fractions to gross disease.

INITIUM regimen using ENI; INITIUM regimen without ENI

ENI RADIATION

Patients receiving ENI will be treated to 5.4 Gy daily to the elective nodal basins for 5 fractions concurrent with treatment to gross disease.

INITIUM regimen using ENI

Surgery PROCEDURE

Patients will be scheduled for surgery at ten weeks (-7 days) after radiation to allow for maximal tumor regression and healing of any radiation-related mucositis. Surgical resection will be tailored to the treatment response.

INITIUM regimen using ENI; INITIUM regimen without ENI

Eligibility Criteria

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

You may qualify if:

• Patients 18 years or older.
• Patients with surgically resectable squamous cell carcinoma of the oral cavity or HPV-negative squamous cell carcinoma of the oropharynx. Resectability will be determined by the treating surgeon. Patients must have locoregionally advanced disease defined by clinical T3-4 staging and/or clinical node positive staging.
• A CPS score of at least 1 on initial biopsy.
• Zubrod, or Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Pregnancy. It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
• Female patients must meet one of the following:
• Postmenopausal for at least one year before the screening visit, OR
• Surgically sterile (i.e., undergone a hysterectomy or bilateral oophorectomy), OR
• If subject is of childbearing potential (defined as not satisfying either of the above two criteria):
• Agree to practice two effective methods of contraception (combination methods requires use of two of the following: diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male or female condom, hormonal contraceptive, intrauterine device, etonogestrel implant, etc.) from the time of signing of the informed consent form through 90 days after the last dose of study agent, AND
• Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptom-thermal, post ovulation methods\] and withdrawal are not acceptable contraception methods).
• Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
• Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
• Must also adhere to the guidelines of any study-specific pregnancy prevention program, if applicable, OR

You may not qualify if:

• HPV-positive squamous cell carcinoma of the oropharynx.
• Tumor inaccessible for clinic-based biopsy as determined by the treating surgeon.
• Solid organ transplant requiring chronic immunosuppression.
• Autoimmune disease requiring use of steroids or chronic immunosuppression.
• Prior invasive malignancy within the past 3 years (except for T1a surgically treated melanoma with negative margins, any early-stage non-melanomatous skin cancer, early-stage prostate cancer, or differentiated thyroid cancer). Patients with benign non-metastasizing tumors are eligible.
• Life expectancy less than 12 months.
• Performance status Zubrod ≥ 3.
• Patients with prior external beam radiation therapy (RT) to the head and neck that overlaps the expected treatment fields.
• a. Note: Patients receiving prior Iodine-131 therapy will be eligible.
• Prior systemic therapy, including cytotoxic chemotherapy, biologic/targeted therapy, or immune therapy for the study cancer.
• Body weight ≤ 30 kg.
• Any of the following severe laboratory abnormalities within 30 days of registration, unless corrected prior to it:
• Sodium \< 125 mmol/L or \> 155 mmol/L
• Potassium \< 3.5 mmol/L or \> 6 mmol/L
• Glucose \> 400 mg/dl

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Interventions

pembrolizumab; Radiotherapy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Musaddiq Awan, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Upon enrollment, patients will be randomized in a 1:1 ratio to either the ENI arm or the no-ENI arm. To maintain blinding, block randomization will be allocated by the study biostatistician with direct communication to the treating radiation oncologist. In case of inability to contact the study biostatistician, the randomization will be stored in the cloud with password-only access available to the study biostatistician and study radiation oncologists. Patients and all other study staff and investigators will be blinded to ENI or no-ENI treatment allocation. Unblinding will occur following finalization of the pathology evaluation by the surgical pathology team.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 19, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: August 19, 2026

Record last verified: 2026-08

Locations

US (1)