BALSTILIMAB on Viral Clearance in HPV+ Oropharyngeal Cancer Patients

Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. Written informed consent and HIPAA authorization for release of personal healthinformation prior to registration. NOTE: HIPAA authorization may be included in theinformed consent or obtained separately.

2. Histologically or cytologically confirmed squamous cell carcinoma from oropharynx.note: patients with a clinical diagnosis of oropharyngeal cancer, awaiting a biopsyis eligible to consent for prescreening.

3. Stage I-III per AJCC 8th edition

4. Positive p16 immunohistochemistry or HPV testing, or p16/HPV status unknown withpatients having a less than 10 pack-year smoking history

5. Age ≥ 18 years at the time of consent.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for patients whoreceive treatment

7. Persistent detection of cfDNA HPV (≥ 16 copies/mL) in the absence of clinicallyevident disease at 3, 6, or 9 months following definitive treatment (surgery,systemic therapy, and/or radiation therapy).

8. Patients must have adequate hematologic, coagulation, hepatic, and renal functionfor anti-PD1 treatment. this includes:

• ANC >/= 1,500/mm3

• platelet count >/=100,000/mm3

• HgB ≥ 9 g/dL (may be with transfusion)

• Creatinine ≤ 1.5x ULN or creatinine clearance (measured via 24-hour urinecollection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN,a 24-hour urine collection to calculate creatinine clearance must beperformed).

• Total Serum Bilirubin ≤ 1.5 x ULN (Patients with known Gilbert Syndrome, atotal bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)

• SGOT, SGPT ≤ 3 X ULN

• SGOT, SGPT ≤ 5 X ULN

9. Females of childbearing potential must not be breast feeding and must have anegative pregnancy test during screening and 7 days prior to initiation of studytreatment. The patient must agree to use adequate contraception. Note: women will beconsidered post-menopausal if they have been amenorrheic for the past 12 monthswithout an alternative medical cause. The following agespecific requirements mustalso apply: women < 50 years old: they would be considered postmenopausal if theyhave been amenorrheic for the past 12 months or more following cessation ofexogenous hormonal treatments. The levels of luteinizing hormone (LH) andfollicle-stimulating hormone (FSH) must also be in the post-menopausal range (as perthe institution). Women ≥ 50 years old: they would be considered post-menopausal ifthey have been amenorrheic for the past 12 months or more following cessation of allexogenous hormonal treatments, or have had radiation-induced oophorectomy with thelast menses > 1 year ago, or have had chemotherapyinduced menopause with >1 yearinterval since last menses, or have had surgical sterilization by either bilateraloophorectomy or hysterectomy.

10. Non-sterilized males who are sexually active with a female partner of childbearingpotential must use adequate contraception for the duration of the study.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Prior treatment history with anti-PD-1 or anti-PD-L1 therapies are not allowed.

2. Any evidence of severe or uncontrolled systemic diseases, including uncontrolledhypertension and active bleeding diatheses, which in the investigator's opinionmakes it undesirable for the subject to participate in the trial or which wouldjeopardize compliance with the protocol, or active and uncontrolled infectionincluding hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.

3. Judgment by the investigator that the patient should not participate in the study ifthe patient is unlikely to comply with study procedures, restrictions andrequirement.

4. Active rheumatological or autoimmune conditions requiring systemic treatment, suchas steroids.

5. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a priorhistory of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids.