Adding Chemo-immunotherapy or Chemotherapy before Salvage Surgery in Recurrent or Persistent Squamous Cell Carcinoma of the Head and Neck (NRG-HN015, the “NEOPOLIS” Study)

03/17/2026

NRG Oncology recently activated NRG-HN015, also known as the NEOPOLIS study, a phase II trial testing whether the addition of pre-operative systemic therapy (chemotherapy or chemo-immunotherapy) improves outcomes for patients with recurrent or persistent, PD-L1-positive, squamous cell carcinoma of the head and neck who are candidates for salvage surgery. This trial is currently open for patient enrollment.

“Currently, patients with squamous cell carcinoma are treated with surgery or radiation and chemotherapy, but approximately 30-40% of patients will recur, and the majority will recur locoregionally. When this type of cancer returns, we typically offer patients salvage surgery.  However not everyone benefits from this approach, and there are several complications that could result from surgery and impact quality of life. NRG-HN015 was designed to test a neo- adjuvant treatment in an attempt to improve the chances of controlling the cancer over the current standard of care,” stated Nabil Saba, MD, Professor and Vice Chair in the Department of Hematology and Medical Oncology at Emory University School of Medicine and the Principal Investigator of the NEOPOLIS trial.

The NEOPOLIS trial will enroll and stratify patients with recurrent and resectable cancer in the oral cavity, oropharynx, larynx, or hypopharynx after prior definitive radiation and no distant metastases. Patients will be randomly assigned to one of three potential treatment arms. Patients in Arm 1 will receive salvage surgery alone. Patients in Arm 2 will receive two cycles of carboplatin and paclitaxel followed by salvage surgery. Patients in Arm 3 will receive two cycles of carboplatin and paclitaxel with the PD-L1 inhibitor cemiplimab (REGN2810) followed by salvage surgery. Post-operative radiation therapy (PORT) with weekly cisplatin is administered only to patients with high-risk pathologic features, specifically positive margins and/or extranodal extension on the three arms of the study.

The primary endpoint of this study is to determine whether the addition of chemotherapy or chemo-immunotherapy prior to salvage surgery improves investigator-assessed event-free survival (EFS) for patients on this trial. Secondary endpoints include comparing disease-free survival, overall survival, distant metastasis rates, toxicity, surgical complications, radiographic response, and pathological response among the three treatment arms.

This trial also includes exploratory objectives assessing and comparing the clinical outcomes within PD-L1 subgroups and determining the impact of surgical quality benchmarks and oncologic outcomes.

This trial is the first NCTN randomized trial enrolling patients with recurrent HNSCC prior to undergoing salvage surgery.

More information:

More on NRG-HN015 can be found at ClinicalTrials.gov

Protocol documents for NRG-HN015 are available on CTSU.org.

A patient study webpage for this trial is available at NRGOncology.org/HN015

NRG-HN015 Study Overview Interview

Dr. David Lee and Dr. Alexis Narvaez Rojas interviewed NRG-HN015 Principal Investigator, Dr. Nabil Saba on this recently activated trial. Watch on our YouTube channel at www.YouTube.com/@NRGOnc or click play below.