CD40 Agonist and PD-1 Inhibitor in HNSCC

Inclusion Criteria: * 1\. Signed and dated written IRB-approved informed consent. * 2\. Age ≥18 years. * 3\. Body weight \> 30kg * 4\. Human Papillomavirus (HPV)-negative histologically confirmed mucosal squamous cell head and neck cancer (oral cavity, oropharynx, larynx, hypopharynx) for which definitive surgery is planned. Sites other than oropharynx are assumed to be HPV negative unless specifically shown otherwise. Oropharynx HPV status can be determined through p16 or nucleic acid testing (ISH). * 5\. Tumor tissue sample (non-cytology specimen) available prior to Study Treatment, either via archived non-FNA (fine needle aspirate) tumor biopsy specimen or fresh biopsy * 6\. Life expectancy of at least 12 weeks. * 7\. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 /mm3, hemoglobin ≥9.0 g/dL, total serum bilirubin within 1.5 x upper limit of normal (ULN) unless Gilbert's, AST/ALT, within 2.5 x ULN, Albumin ≥3g/dL, and all tests performed within 4 weeks prior to administration of Study Treatment. * 8\. Eastern Cooperative Oncology Group (ECOG) with no clinically significant findings as assessed by the investigator. * 9\. ECOG performance status of 0-1. * 10\. Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after therapy). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Female patients should also refrain from breastfeeding throughout this period. * 11\. Able and willing to comply with all study procedures. Exclusion Criteria: * 1\. Prior history of Head and Neck Squamous Cell Carcinoma (HNSCC) for which patient has undergone surgery or radiation involving the current planned surgical site. 2\. Known history of hepatitis B or C with active viral replication. 3. Administration of any live vaccine within 28 days of first dose of study treatment. 4\. Prior anti-PD1 or CD40 agonist therapy. 5. Participation in another interventional clinical trial within 30 days before receiving first dose of study treatment. However, the subject may participate in observational studies. 6\. Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint. 7\. Current or prior use of immunosuppressive medication within 14 days before study treatment. The following are exceptions to this criterion: a. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent. 8\. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product (IP). 9\. History of allogenic organ transplantation 10. Active or prior documented autoimmune disease. Examples include inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]. The following are exceptions to this criterion: 1. Patients with vitiligo or alopecia 2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or type 1 Diabetes Mellitus (DM) controlled with insulin. 3. Any chronic skin condition that does not require systemic therapy. 4. Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician. 5. Patients with celiac disease controlled by diet alone. 11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 12. History of another active malignancy except for non-melanoma skin cancer, lentigo maligna or other carcinoma in situ 13. History of active primary immunodeficiency. Patients with Human Immunodeficiency Virus (HIV) with undetectable HIV viral loads by standard clinical assays are eligible. 14\. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.