Phase I/ II Trial Combining PD-1 Inhibition and Neoadjuvant Proton or Photon Radiation Therapy in Recurrent Head and Neck Squamous Cell Carcinoma

1. Patients must have histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma including oral cavity, laryngeal, hypopharyngeal, or oropharyngeal (HPV-) SCC.

2. Patients must be a candidate for salvage surgical resection.

3. Patients must have failed prior RT \>6 months prior to recurrence with at least 30 Gy delivered to the current target volume.

4. Disease must be limited to a single site or adjacent sites that can be treated in a single contiguous target volume for which the maximum total tumor dimension (GTV) must be \<7 cm.

5. Patients must have a CPS PD-L1 of ≥1%. This may be tested on a new biopsy or archival tissue.

6. Age ≥18 years.

7. ECOG performance status ≤1 (or Karnofsky ≥70%, see Appendix A).

8. Patients must have adequate organ and marrow function as defined below:

Platelets ≥100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Creatinine ≤ 1.5x institutional upper limit of normal (ULN) OR glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (see Appendix B).

9. Archival tissue must be available for baseline analysis. Either a tumor block or at least 20 slides must be available.

10. Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

11. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

13. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

14. 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. To be eligible for this trial, patients should be class 2B or better.

15. Women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of pembrolizumab administration.

16. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

What this study is about