A Study of Cemiplimab and Fianlimab in People With Nasopharyngeal Carcinoma

Inclusion Criteria: * Age ≥ 18 * Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph node) diagnosis of non-keratinizing nasopharynx carcinoma * Pathologic confirmation of EBV status in biopsy sample. EBER (Epstein-Barr virus-encoded RNA) detection via immunohistochemistry or in situ hybridization or polymerase chain reaction, collected as routine clinical standard to determine EBV status. * Patient must be seen by head and neck surgery, radiation oncology, medical oncology, as standard of care which includes standard nasopharyngoscopy. All three disciplines need to agree that the patient is eligible. Note: Nasopharyngoscopy does not need to be repeated by all three disciplines. This test is often only performed by head and neck surgery and/or radiation oncology. * AJCC 8th edition: T1N1, T2N0-1, T1-T2N2 nasopharynx carcinoma * ECOG performance status 0-1 * Adequate organ and bone marrow function documented by: * Hemoglobin \> 9.0 g/dL * Absolute neutrophil count (ANC) \>1.5 x 109 /L * Platelet count \>100 x 109 /L * Adequate renal function: Serum creatinine \<1.5 mg/dL or creatinine clearance ≥ 50 ml/min determined by 24-hour urine collection or estimated by Cockcroft-Gault formula * Adequate hepatic function: - T bili \<1.5x ULN, AST or ALT \< 1.5 ULN, Alkaline phosphatase \<1.5 x ULN). Note: for patients with Gilbert Syndrome, total Bilirubin \<3x ULN. * Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential * Signed informed consent form by the participant. Exclusion Criteria: \- Evidence of distant metastatic disease by radiographic imaging. Equivocal findings are subject to P.I. and Co-PI approval * Prior head and neck radiation (Exceptions can be made if the overlap regions are minimal and must be approved by PI/Co-PI) * Grade ≥2 hearing loss * Grade ≥2 peripheral sensory neuropathy * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years is 90% or greater o Note: Exceptions can be made for patients with prior or concurrent invasive malignancy if determined by the PI/Co-PI, then the patient can proceed with protocol activities * Prior systemic chemotherapy for the study cancer o Note: prior chemotherapy for a different cancer is allowable, must check with PI/Co-PI * Severe, active co-morbidity defined as follows: o Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics treatment within 2 weeks prior to the first dose of trial medication * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects * Lack of ability to understand and willingness to sign a written informed consent and complete questionnaires. * Participants with a history of myocarditis. * TnT or troponin I TnI \> 2x institutional ULN at baseline. Patients with TnT or TnI levels between \> 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are \> 1 to 2x ULN within 24 hours, the patient may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest. * History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication. * Uncontrolled infection with HIV, HBV, or HCV infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. o Patients with known HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection, monitoring will be performed per local standards. * Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug. * Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted. * Patients with HIV or hepatitis must be reviewed by a qualified specialist (e.g., infectious disease or hepatologist) managing this disease prior to commencing and regularly throughout the duration of their participation in the trial * Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment. * Known hypersensitivity to the active substances or to any of the excipients. * Patients using immunosuppressive doses (≥10 mg per day of prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement will not be eligible for the study. * Received a live vaccine within 30 days of planned start of study medication, during treatment and for 90 days after treatment. o Live or live attenuated vaccination with replicating potential. If a patient intends to receive a COVID-19 vaccine before the start of study drug, participation in the study should be delayed at least 1 week after any COVID-19 vaccination. During the treatment period, it is recommended to delay COVID-19vaccination until patients are receiving and tolerating a steady dose of study drug. A vaccine dose should not be less than 48 hours before or after study drug dosing. * Woman of child bearing potential (WOCBP)\* must have a negative serum (beta-hCG) within 14 days prior to registration. * \*WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. * Pregnancy testing and contraception are not required for women who are post-menopausal or permanently sterile. * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation * Male study participants with WOCBP partners are required to use condoms during the study and until 6 months after the last dose of study treatment unless they are vasectomized or practice sexual abstinence† * Vasectomized partner or vasectomized study participant must have received medical assessment of the surgical success. * Periodic abstinence‡, withdrawal (coitus interruptus), spermicides only, and LAM are not acceptable methods of contraception. Female condom and male condom should not be used together. * WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment * All men must agree not to donate sperm during the trial and for 6 months after receiving the last therapy dose * Pregnant or breastfeeding women. o WOCBP who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include: i. stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; ii. intrauterine device; intrauterine hormone-releasing system; iii. bilateral tubal occlusion/ligation; iv. vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or v. sexual abstinence† ‡ * Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. * Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and LAM are not acceptable methods of contraception. Female condom and male condom should not be used together.