Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of squamous-cell carcinoma of the
             oropharynx or of an upper (levels 2-3) neck mass without a known primary site, but is
             suspected to be oropharynx based on clinical factors.

          -  Stage I-III (AJCC 8th Edition) [except clinical stages T1N0 and T2N0, which are
             excluded from enrollment].

          -  A candidate for standard of care therapy (either surgery followed by adjuvant therapy
             OR def-CRT), based on treating physician decision.

          -  HLA-A*0201 genotype as determined by genomic testing on blood sample performed at a
             CLIA-certified clinical or central laboratory.

          -  Tumors must test positive for HPV16 by ISH and p16INK4A expression (>70% staining in
             tumor cells) by IHC performed at a CLIA-certified clinical or central laboratory.

          -  Have archival tumor tissue sample or newly obtained core or excisional biopsy of a
             tumor lesion of sufficient size and quality for eligibility determination.

          -  At least 18 years of age.

          -  ECOG performance status ≤ 1.

          -  Normal bone marrow and organ function as defined below:

               -  Platelets ≥ 100,000/mcl

               -  Hemoglobin ≥ 9.0 g/dL

               -  Absolute neutrophil count ≥ 1,500/mcl

               -  AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

               -  Total bilirubin ≤ 1.5 x IULN, except patients with Gilbert's syndrome, who may
                  enroll if the conjugated bilirubin (total and direct) is within normal limits

               -  Creatinine > 1.5 mg/dL, or calculated or measured creatinine clearance >30 mL/min
                  by Cockcroft-Gault

               -  Note: Screening laboratory tests may be repeated once within 7 days.

          -  The effects of CUE-101 on the developing human fetus are unknown. For this reason and
             because novel Fc Fusion Protein agents are known to be teratogenic, women of
             childbearing potential and men must agree to use adequate contraception (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 participating in this study, she must 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 the study, and 30 days after completion of the
             study.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable) prior to
             initiation of any study-related tests or procedures that are not part of SOC for the
             patient's disease.

        Exclusion Criteria:

          -  History of prior allogeneic bone marrow, stem-cell or solid organ transplantation

          -  Distant metastases.

          -  Treatment with radiation therapy or systemic anti-cancer therapy prior to the
             initiation of study drug administration.

          -  Treatment with corticosteroids (>10 mg per day prednisone or equivalent) or other
             immune suppressive drugs within the 14 days prior to the initiation of study drug
             administration. Corticosteroids for topical, ophthalmic, inhaled, or nasal
             administration are allowed. Physiological replacement with hydrocortisone up to a
             maximum dose of 40 mg per day is allowed.

          -  History of clinically significant cardiovascular disease including:

               -  Myocardial infarction or unstable angina within the 16 weeks prior to the
                  initiation of study drug

               -  Clinically significant cardiac arrhythmias

               -  Uncontrolled hypertension: systolic blood pressure >180 mmHg, diastolic blood
                  pressure >100 mmHg

               -  Deep vein thrombosis, pulmonary embolism, stroke, or transient ischemic attack
                  within the 16 weeks prior to the initiation of study drug

               -  QTc prolongation > 480 msec

               -  Congestive heart failure (New York Heart Association class III- IV)

               -  Pericarditis/clinically significant pericardial effusion

               -  Myocarditis

          -  Clinically significant pulmonary compromise (eg, requirement for supplemental oxygen).

          -  Clinically significant gastrointestinal (GI) disorders including history of:

               -  GI perforation within 1 year prior to study drug administration;

               -  GI bleeding within 3 months prior to the initiation of study drug;

               -  Acute pancreatitis within 3 months prior to the initiation of study drug;

               -  Diverticulitis that is clinically significant in the opinion of the investigator
                  based on the extent or severity of known disease and/or the occurrence of
                  clinically significant disease flares within 4 weeks prior to the initiation of
                  study drug administration; and/or

               -  Cirrhosis.

          -  Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral
             treatment within 7 days prior to the initiation of study drug. Patients requiring any
             systemic antiviral, antifungal, or antibacterial therapy for active infection must
             have completed treatment no less than 1 week prior to the initiation of study drug.

          -  Known history of hepatitis B or hepatitis C infection or known positive test for
             hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain
             reaction. However, patients with treated hepatitis C in complete remission and off
             therapy for > 1 year are eligible.

          -  Second primary invasive malignancy that has not been in remission for greater than 2
             years. Exceptions include: non-melanoma skin cancer; cervical carcinoma in situ;
             squamous intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score
             < 6); resected melanoma in situ; or favourable prognosis (<10% relapse risk) thyroid
             cancer.

          -  Prior treatment of the head and neck region with radiation therapy.

          -  History of major surgery within 4 weeks prior to the initiation of study drug
             administration. A diagnostic needle or excisional biopsy is not considered major
             surgery.

          -  Any serious underlying medical condition that would impair the ability of the patient
             to receive or tolerate the planned treatment at the investigational site.

          -  Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient
             contained in the drug formulation for CUE-101.

          -  Vaccination with any live virus vaccine within 4 weeks prior to the initiation of
             study drug administration. Inactivated annual influenza vaccination is allowed.
             Vaccination for COVID-19 is allowed within one week prior to initiation of study drug
             administration.

          -  Active or recent history of uncontrolled alcohol or other substance abuse within 3
             months prior to the initiation of study drug administration.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             serum pregnancy test within 72 hours of study entry.