The completion of the form is strongly recommended but is not required. 3.CT of neck and chest. In cases where a CT is not clinically appropriate, other imaging modalities such as MRI may be used as clinically appropriate. 4.Vital signs will be obtained routinely as part of ‘physical’ exam. Additionally, on D1 and D15 (treatment days) vital signs will be obtained at the beginning of and at the end of M7824 infusion. 5.Mandatory biopsy performed within 5 days prior to day 1 of treatment 6.Optional research biopsy performed if patient not having surgery at NIH Clinical Center or Suburban Hospital. If patient having surgery at NIH or Suburban hospital, tissue samples will be obtained from the OR. 7.1,200 mg of M7824 via IV infusion on day 1 and day 15. For the prevention of possible allergic reactions, patients may receive an antihistamine such as Benadryl and acetaminophen (Tylenol) before the M7824 infusion. See section 8.Dosing and administration as described in section 3.2.3. 9.N-803 (15mcg/kg) subcutaneous injection on day 1 10.Chemistry: Serum, Acute care panel, Hepatic panel and Mineral panel. Please refer section 2.2 and 2.4 for details. 11.Applies to females of childbearing potential only (within 3 days prior to enrollment) 12.Patients who have had HLA Class I typing previously performed at NIH do not require retesting. 13.For correlative studies: Blood sample will be collected on days 1 and 15 prior giving treatment, Additionally, When no treatment is being given, blood will be collected around day 8 (may occur anytime from days 6-10), within day 21-28, and around day 105. This could occur +/- 3 days for any time point. Please refer to section 5.1 for details. Per PI discretion additional samples might be collected at the NIH Clinical Center every 12 weeks while on study and at the time of taking a patient off treatment. 14.Will occur +/- 7 days for every two-week mark up to day 105. 15.Will occur +/- 2 weeks of day 105. 16.Starting 3 months after the day 105 visit, every 3 months (+/- 1 week), patients will be contacted by phone call or e- mail for questioning regarding disease progression, adverse events, and survival until the patient is 2 years out from surgery. Only AEs considered related to study treatment will be collected as explained in detail under Section 6.1. 37 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 17.Visit and labs are to be performed on day 49 (+21/- 7 days). Flexibility on timing is provided because, depending on tumor location and extent of surgery, patients commonly remain in the hospital for several weeks post-operatively. This visit may be skipped per investigator discretion. 18.Medical history, physical exam and clinical labs may be performed/drawn within 4 days prior to the day 15 treatment 19.Visualization of tumor with Clinic-based flexible nasopharyngo-laryngoscopy may be deferred in patients whose primary tumors are accessible without these procedures. Nasopharyngo-laryngoscopy done for research purposes may also be deferred in cases where institutional facility procedures are prohibitive (e.g., the appropriate clinical setting is not available due pandemic-related restrictions). 20.PTT/PT may be omitted 21.Procedures are to be performed once within this timeframe 38 Abbreviated Title: Neoadjuvant IO for HNSCC Version Date: August 31, 2022 3.5 COST AND COMPENSATION 3.5.1 Costs NIH does not bill health insurance companies or participants for any research or related clinical care that participants receive at the NIH Clinical Center. If some tests and procedures are performed outside the NIH Clinical Center, participants may have to pay for these costs if they are not covered by an insurance company.