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

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)

Phase 2 Interventional National Cancer Institute (NCI) · NCT07195734

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
Enrollment180 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionschemotherapy, immunotherapy, radiation, cemiplimab
Locations48 sites (Tucson, Arizona and 47 other locations)
Trial IDNCT07195734 on ClinicalTrials.gov

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.

Who should consider this trial

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.

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.

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 performed: 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.

Eligibility criteria

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 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 this trial is running

Tucson, Arizona and 47 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Clinical Stage II HPV-Mediated Oropharyngeal Carcinoma AJCC v8Clinical Stage III HPV-Mediated Oropharyngeal Carcinoma AJCC v8Locally Recurrent Head and Neck Squamous Cell CarcinomaLocally Recurrent Hypopharyngeal Squamous Cell CarcinomaLocally Recurrent Laryngeal Squamous Cell CarcinomaLocally Recurrent Oral Cavity Squamous Cell CarcinomaLocally Recurrent Oropharyngeal Squamous Cell CarcinomaStage II Laryngeal Cancer AJCC v8
Last reviewed 2026-06-13 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.