Nivolumab + Chemoradiation in Stage II-IVB Nasopharyngeal Carcinoma (NPC)

Inclusion Criteria:

1. Males and females ≥18 years of age.

2. Histologically or cytologically confirmed nasopharyngeal carcinoma, stage II-IV byAmerican Joint Committee on Cancer (AJCC) 7th edition, endemic-type (defined asWorld Health Organization (WHO) type 2a and 2b nonkeratinizing or undifferentiatedsubtypes, excluding WHO type I keratinizing subtype) performed on a biopsy thatoccurred within 90 days of registration.

3. Positron emission tomography-computed tomography (PET-CT) (preferred) or a CT ofchest, abdomen, and pelvis within 60 days of registration showing radiographic stageII to IVB nasopharyngeal cancer.

4. No distant metastasis as verified by one of the study investigators.

5. Documentation that the patient is a candidate for chemoradiation of theirnasopharyngeal cancer by one of the study investigators.

6. Ability to tolerate radiation therapy (e.g. lie flat and hold position fortreatment).

7. Measurable disease as defined by RECIST v1.1.

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

9. Lack of contraindications to systemic immunotherapy (see list of exclusions below).

10. Resolution of all acute toxic effects of any prior chemotherapy, radiotherapy orsurgical procedures to NCI CTCAE Version 5.0 grade 1.

11. Adequate hepatic, hematologic, and renal indices permitting administration ofcisplatin and nivolumab (within 14 days of registration): Hepatic Function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upperlimit of normal (ULN); Total bilirubin ≤ 1.5 × ULN (except subjects with GilbertSyndrome, who can have total bilirubin < 3.0 mg/dL) Adequate bone marrow function: White blood cells (WBC) ≥ 2000/μL Neutrophils ≥ 1500/μL Platelet ≥ 100 x103/μLHemoglobin > 9.0 g/dL Adequate renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) OR Creatinine clearance (CrCl) > 40 mL/min (or > 50 mL/min for Singapore sites only) (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine inmg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatininein mg/dL

12. Women of childbearing potential must have a negative serum pregnancy test within 24hours prior to the first dose of study treatment and agree to use appropriate highlyeffective methods of contraception, during the study and for 5 months followingcompletion of study treatment; A "Woman of childbearing potential" is defined as anyfemale who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause isdefined clinically as 12 months of amenorrhea in a woman over 45 in the absence ofother biological or physiological causes. In addition, women under the age of 62must have a documented serum follicle stimulating hormone (FSH) level less than 40milli-international units per milliliter (mIU/mL). Female Subjects: Women of child bearing potential are expected to use one of the highly effectivemethods of contraception listed in the protocol. Male Subjects: Male subjects must inform their female partners who are women of child bearingpotential of the contraceptive requirements and are expected to adhere to usingcontraception with their partner. Female partners of male subjects, who are women ofchild bearing potential, are expected to use one of the highly effective methods ofcontraception listed in the protocol. In addition, male subjects are expected to usea condom as noted in the protocol.

13. Men with a female partner of childbearing potential must agree to use highlyeffective methods of contraception or any contraceptive method with a failure rateof less than 1% per year during the study and for 7 months following completion ofstudy treatment.

14. Ability to sign informed consent.

Exclusion Criteria:

1. Active second malignancy, i.e. patient known to have potentially fatal hematologicmalignancy or another solid primary tumor present for which he/she may be (but notnecessarily) currently receiving treatment. Patients with a prior or concurrentmalignancy whose natural history or treatment does not have the potential tointerfere with the safety or efficacy assessment of the investigational regimen areallowed to enroll in this trial. For example, patients with early-stage skincancers, prostate cancer under surveillance with non-rising prostate-specificantigen (PSA), or meningioma or thyroid papillary cancers which are undersurveillance are eligible. For determinations of a specific clinical condition,please consult with the Principal Investigator.

2. Active, untreated central nervous system (CNS) metastases;

3. Prior treatment with any other anti-programmed cell death protein-1 (anti-PD-1), orPD Ligand-1 (PD-L1) or PD Ligand-2 (PD-L2), anti-cytotoxic T-lymphocyte-associatedprotein-4 (CTLA-4) antibody, or any other antibody or drug specifically targetingT-cell costimulation or immune checkpoint pathways, or cancer vaccine;

4. Prior systemic cytotoxic therapy, antineoplastic biologic therapy, or major surgerywithin 28 days of first dose of study medication;

5. Severe hypersensitivity reaction to treatment during prior administration of amonoclonal antibody (mAb) or history of allergy to any study drug component;

6. Has received a live-virus vaccination within 30 days of planned treatment start;

7. Condition requiring systemic treatment with either corticosteroids (> 10 mg dailyprednisone equivalents) or other immunosuppressive medications within 14 days ofstudy drug administration; Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of activeautoimmune disease.

8. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a priorhistory of ILD or pneumonitis requiring oral or IV glucocorticoids;

9. Active, known, or suspected autoimmune disease or any autoimmune condition that hasrequired systemic treatment in the past 2 years (replacement therapies for hormonedeficiencies are allowed); Subjects are permitted to enroll if they have vitiligo,type I diabetes mellitus, residual hypothyroidism due to autoimmune condition onlyrequiring hormone replacement, psoriasis not requiring systemic treatment, orconditions not expected to recur in the absence of an external trigger.

10. Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI)obstruction, or abdominal carcinomatosis (known risks factors for bowelperforation);

11. Signs or symptoms of infection within 2 weeks prior to first day of study treatment.

12. Patients with active tuberculosis (clinical evaluation in line with local practice),or a known history of active tuberculosis that in the opinion of the treatinginvestigator has a high risk of reactivation.

13. Received therapeutic oral or IV antibiotics within 2 weeks prior to first day ofstudy treatment: Patients receiving prophylactic antibiotics (eg, to prevent aurinary tract infection or chronic obstructive pulmonary disease exacerbation) areeligible.

14. Known positive test for human immunodeficiency virus (HIV);

15. Known active hepatitis B or hepatitis C virus (HBV or HCV): Patients with past orresolved HBV infection (defined by a negative hepatitis B surface antigen (HBsAg)test and a positive anti-hepatitis B core antigen (HBc) (anti-HBc)antibody test) areeligible. HBV DNA must be obtained in these patients prior to first day of studytreatment. Patients who have been recently discovered to have HBV with positiveHBsAg test and positive anti-HBc antibody test but who have been started onantiretroviral treatment with nondetectable HBV DNA are eligible. HBV DNA must beobtained in these patients prior to first day of study treatment

16. Patients with known active hepatitis C virus ribonucleic acid (HCV antibody)indicating acute or chronic infection: Patients positive for HCV antibody areeligible only if Polymerase chain reaction (PCR) test is negative for HCV RNA.

17. Prior radiation therapy of any type within 7 days of first dose of study medication;

18. Prior radiation therapy to head and neck region that would overlap with intendedradiation treatment for nasopharyngeal carcinoma;

19. Medical contraindication to radiation treatment (e.g. active systemic sclerosis,other uncontrolled autoimmune condition)

20. Treatment with prohibited medications (including concurrent anticancer therapyincluding chemotherapy, radiation, hormonal treatment [except corticosteroids andmegestrol acetate] ≤ 14 days prior to treatment.

21. Pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the study;

22. Active, uncontrolled psychiatric disorders or substance (drug/alcohol) abuse thatinterfere with patient's safety, ability to provide informed consent, or ability tocomply with the protocol.

23. Persons who are incarcerated or otherwise under compulsory detention by an authorityare not eligible.