Clinical trial Recruiting at 114 sites Phase 2 Interventional Ages 18 and up

Adding chemotherapy or chemo-immunotherapy to standard salvage surgery for advanced head and neck cancer

Official title: A Phase II Randomized Trial of Neoadjuvant Chemotherapy or Chemo-Immunotherapy in Patients With Recurrent/Persistent PD-L1 Enriched Squamous Cell Carcinoma of the Head and Neck Undergoing Salvage Surgery (NEOPOLIS)

Run by National Cancer Institute (NCI) · NCT07195734 · Data updated 2026-11-12

This trial tests whether giving chemotherapy alone or chemotherapy plus the immunotherapy cemiplimab before salvage surgery helps people with PD-L1–positive recurrent or persistent head and neck squamous cell carcinoma.

Quick facts

PhasePhase 2
Study typeInterventional
Ages18 Years and up
SexAll
Enrollment180 (estimated)
SponsorNational Cancer Institute (NCI)
NIH
Drugs / interventionschemotherapy, immunotherapy, radiation, prednisone, cemiplimab
Locations115 sites (Tucson, Arizona and 114 other locations)
StatusRecruiting
StartedApril 24, 2026
Main results expectedFebruary 1, 2033
Study endsFebruary 1, 2033
Registry record updatedOctober 26, 2026
Trial IDNCT07195734 on ClinicalTrials.gov

Is this trial a fit for you?

Likely a good fit

Patients with locally recurrent or persistent, PD-L1–positive squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx who are candidates for salvage surgery and have measurable disease are the intended participants.

Probably not a fit

People whose tumors are PD-L1 negative, who have unresectable or distant metastatic disease, who cannot tolerate chemotherapy or immunotherapy, or who lack measurable disease are unlikely to benefit from this protocol.

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized phase II trial compares standard salvage surgery (with adjuvant radiation and cisplatin for high-risk patients) to two neoadjuvant approaches using carboplatin plus paclitaxel, with or without the PD‑1 antibody cemiplimab, given before surgery. Patients are randomized to one of three arms and are followed for event-free survival as the primary outcome, with disease-free survival, overall survival, distant metastasis, toxicity, and radiographic and pathologic response as key secondary measures. Exploratory analyses will examine outcomes by PD-L1 combined positive score subgroups and the impact of surgical quality metrics. Eligible patients have locally recurrent or persistent, resectable squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx and a PD-L1 CPS ≥ 1.

Why it matters

Potential benefit: If successful, the approach could reduce recurrence and improve event-free survival by shrinking tumors before surgery and activating the immune response.

How similar studies have gone: Neoadjuvant chemotherapy and PD‑1 blockade have shown promising pathologic and radiographic responses in other head and neck cancer studies, but clear survival benefits are not yet established and this exact combination remains under investigation.

Who can join: the full rules

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Pathologically (histologically or cytologically) proven diagnosis of locally recurrent or persistent squamous cell carcinoma of head and neck (SCCHN) arising within the oral cavity, oropharynx, larynx, or hypopharynx
* PD-L1 combined positive score (CPS) ≥ 1 using a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
* Verify insurance (or other payment) coverage for neoadjuvant chemotherapy
* Measurable disease as defined by RECIST 1.1
* Patients must have locally recurrent or persistent SCCHN arising within the oral cavity, oropharynx, larynx, or hypopharynx (American Joint Committee on Cancer \[AJCC\] Cancer Staging Manual, 8th Edition) AND are deemed candidates for salvage surgery:

  * P16 positive oropharynx patients with T2, T3, T4, N0, N1, N2 and all other patients with T2, T3, T4a, N0, N1, N2a, N2b, N2c, N3a are eligible.
  * Patients must be deemed surgically resectable without gross residual disease.
  * For patients with oral cavity SCCHN, only those with recurrent or persistent disease after prior surgery are eligible.
  * Patients who are candidates for salvage laryngectomy to treat recurrent laryngeal cancer and who are having salvage surgery for curative intent are eligible.
  * Patients with resectable lymph node-only recurrence are eligible.
  * No major vascular involvement (\> 180° involvement of the common carotid or internal carotid artery), jugular foramen involvement, or prevertebral, paraspinous muscle involvement precluding a curative resection
* No evidence of distant metastatic disease
* The following minimum diagnostic workup is required:

  * General history and physical examination.
  * Diagnostic-quality neck CT and PET/CT of neck (PET with attenuation-correction CT of neck, chest, and abdomen)
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 30 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dL is acceptable)
* Adequate renal function defined as creatinine clearance (CrCL) \> 50 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (Not applicable to patients with known Gilbert's syndrome)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* Only patients who received prior radiation therapy in the definitive or post-operative setting (limited to one course) are eligible.

  * Prior radiation therapy must have been completed at least 6 months prior to registration with the majority of the index persistent/recurrent cancer volume (\> 50%) irradiated to ≥ 40 Gy at the time
* Prior systemic therapy including immunotherapy with anti-PD1 or anti-PDL1 within the definitive setting (neo-adjuvant, or adjuvant) is permitted and must have been completed at least 4 months prior to registration
* Prior systemic therapy including immunotherapy for treatment of recurrent or metastatic SCCHN is not permitted
* No investigational anti-cancer agents received within 4 weeks prior to registration
* No New York Heart Association Functional Classification III or IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification)
* No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments
* No peripheral neuropathy grade 3 or 4
* No history of interstitial lung disease
* No active, noninfectious pneumonitis requiring immunosuppressive therapy
* No history of a solid organ transplant (other than corneal transplant)
* No active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease-modifying agents, corticosteroids \[\> 10 mg prednisone/day or equivalent\] or immunosuppressive drugs)

  * NOTE: Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:

    * Patients who require a brief course of steroids (e.g., prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
    * Patients with type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
    * Physiologic replacement doses ≤ 10 mg prednisone/day or equivalent are allowed. Inhaled or topical steroids are permitted
* No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent, and immune checkpoint inhibitors (or any of its excipients)

Where it's running

  • Banner University Medical Center - Tucson
    Tucson, Arizona, United States
    Recruiting
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona, United States
    Recruiting
  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
    Irvine, California, United States
    Recruiting
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California, United States
    Recruiting
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, United States
    Recruiting
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California, United States
    Recruiting
Show 44 more locations
  • Sutter Medical Center Sacramento
    Sacramento, California, United States
    Recruiting
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, United States
    Recruiting
  • Emory Proton Therapy Center
    Atlanta, Georgia, United States
    Recruiting
  • Emory University Hospital Midtown
    Atlanta, Georgia, United States
    Recruiting
  • Northwestern University
    Chicago, Illinois, United States
    Recruiting
  • Rush MD Anderson Cancer Center
    Chicago, Illinois, United States
    Recruiting
  • Carle at The Riverfront
    Danville, Illinois, United States
    Recruiting
  • Northwestern Medicine Cancer Center Kishwaukee
    DeKalb, Illinois, United States
    Recruiting
  • Carle Physician Group-Effingham
    Effingham, Illinois, United States
    Recruiting
  • Northwestern Medicine Cancer Center Delnor
    Geneva, Illinois, United States
    Recruiting
  • Northwestern Medicine Glenview Outpatient Center
    Glenview, Illinois, United States
    Recruiting
  • Northwestern Medicine Grayslake Outpatient Center
    Grayslake, Illinois, United States
    Recruiting
  • Northwestern Medicine Lake Forest Hospital
    Lake Forest, Illinois, United States
    Recruiting
  • Rush MD Anderson Cancer Center at Rush Lisle
    Lisle, Illinois, United States
    Recruiting
  • Carle Physician Group-Mattoon/Charleston
    Mattoon, Illinois, United States
    Recruiting
  • Northwestern Medicine Oak Brook
    Oak Brook, Illinois, United States
    Recruiting
  • Northwestern Medicine Orland Park
    Orland Park, Illinois, United States
    Recruiting
  • Memorial Hospital East
    Shiloh, Illinois, United States
    Recruiting
  • Carle Cancer Center
    Urbana, Illinois, United States
    Recruiting
  • Northwestern Medicine Cancer Center Warrenville
    Warrenville, Illinois, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    Ankeny, Iowa, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    Clive, Iowa, United States
    Recruiting
  • Iowa Methodist Medical Center
    Des Moines, Iowa, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    Des Moines, Iowa, United States
    Recruiting
  • Broadlawns Medical Center
    Des Moines, Iowa, United States
    Recruiting
  • Mercy Medical Center - Des Moines
    Des Moines, Iowa, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Laurel Clinic
    Des Moines, Iowa, United States
    Recruiting
  • UI Health Care Mission Cancer and Blood - Waukee Clinic
    Waukee, Iowa, United States
    Recruiting
  • University of Kansas Cancer Center
    Kansas City, Kansas, United States
    Recruiting
  • University of Kansas Cancer Center-Overland Park
    Overland Park, Kansas, United States
    Recruiting
  • University of Kansas Hospital-Westwood Cancer Center
    Westwood, Kansas, United States
    Recruiting
  • LSU Health Baton Rouge-North Clinic
    Baton Rouge, Louisiana, United States
    Recruiting
  • Our Lady of the Lake Physician Group
    Baton Rouge, Louisiana, United States
    Recruiting
  • Our Lady of The Lake
    Baton Rouge, Louisiana, United States
    Recruiting
  • Lafayette Family Cancer Center-EMMC
    Brewer, Maine, United States
    Recruiting
  • University of Michigan Rogel Cancer Center
    Ann Arbor, Michigan, United States
    Recruiting
  • University of Michigan - Brighton Center for Specialty Care
    Brighton, Michigan, United States
    Recruiting
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan, United States
    Recruiting
  • Henry Ford Hospital
    Detroit, Michigan, United States
    Recruiting
  • Weisberg Cancer Treatment Center
    Farmington Hills, Michigan, United States
    Recruiting
  • University of Mississippi Medical Center
    Jackson, Mississippi, United States
    Recruiting
  • Siteman Cancer Center at Saint Peters Hospital
    City of Saint Peters, Missouri, United States
    Recruiting
  • Siteman Cancer Center at West County Hospital
    Creve Coeur, Missouri, United States
    Recruiting
  • University of Kansas Cancer Center - Briarcliff
    Kansas City, Missouri, United States
    Recruiting

+65 more sites. See ClinicalTrials.gov for the full list.

Study contacts

  • Principal investigator: Nabil F Saba — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

How to take part

  1. Review the eligibility criteria above with your treating physician.
  2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
  3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.
Last reviewed 2026-11-14 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.