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

Inclusion Criteria

• Males and females ≥18 years of age.
• Histologically or cytologically confirmed nasopharyngeal carcinoma, stage II-IV by American Joint Committee on Cancer (AJCC) 7th edition, endemic-type (defined as World Health Organization (WHO) type 2a and 2b nonkeratinizing or undifferentiated subtypes, excluding WHO type I keratinizing subtype) performed on a biopsy that occurred within 90 days of registration.
• Positron emission tomography-computed tomography (PET-CT) (preferred) or a CT of chest, abdomen, and pelvis within 60 days of registration showing radiographic stage II to IVB nasopharyngeal cancer.
• No distant metastasis as verified by one of the study investigators.
• Documentation that the patient is a candidate for chemoradiation of their nasopharyngeal cancer by one of the study investigators.
• Ability to tolerate radiation therapy (e.g. lie flat and hold position for treatment).
• Measurable disease as defined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Lack of contraindications to systemic immunotherapy (see list of exclusions below).
• Resolution of all acute toxic effects of any prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE Version 5.0 grade 1.
• Adequate hepatic, hematologic, and renal indices permitting administration of cisplatin and nivolumab (within 14 days of registration):

Hepatic Function:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 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 in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

• Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the first dose of study treatment and agree to use appropriate highly effective methods of contraception, during the study and for 5 months following completion of study treatment; A "Woman of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 milli-international units per milliliter (mIU/mL).

Female Subjects:

Women of child bearing potential are expected to use one of the highly effective methods of contraception listed in the protocol.

Male Subjects:

Male subjects must inform their female partners who are women of child bearing potential of the contraceptive requirements and are expected to adhere to using contraception with their partner. Female partners of male subjects, who are women of child bearing potential, are expected to use one of the highly effective methods of contraception listed in the protocol. In addition, male subjects are expected to use a condom as noted in the protocol.

• Men with a female partner of childbearing potential must agree to use highly effective methods of contraception or any contraceptive method with a failure rate of less than 1% per year during the study and for 7 months following completion of study treatment.
• Ability to sign informed consent.

Exclusion Criteria

• Active second malignancy, i.e. patient known to have potentially fatal hematologic malignancy or another solid primary tumor present for which he/she may be (but not necessarily) currently receiving treatment. Patients w