Concurrent Chemoradiation and Durvalumab for Locoregionally Advanced Nasopharyngeal Carcinoma

Inclusion Criteria: 1. Patients must have pathologically confirmed, previously untreated stage III-IVA nasopharyngeal carcinoma (staged by American Joint Committee on Cancer/Union International for Cancer Control 8th edition staging classification) who plan to receive radical chemoradiation +/- durvalumab. 2. Fresh frozen tumour and archived formalin-fixed paraffin-embedded (FFPE) nasopharyngeal tumour specimens must be available for PD-L1 expression and/other biomarker correlation studies. 3. Age between 18-75 years. (The age limit set at 75 years because a previous Hong Kong study showed that elderly patient \>70 years had poor tolerance to radiotherapy and worse survival for their NPC. Please refer to Sze et al. Radical radiotherapy for nasopharyngeal carcinoma in elderly patients: The importance of co-morbidity assessment Oral Oncology 2012;48:162-167.) 4. Eastern Cooperative Oncology Group Performance Status of 0 or 1 5. All eligible patients must be magnetic resonance imaging of T1, T2 and T1-contrast enhanced sequences of the head and neck region and PET-CT scan within 60 days of study entry 6. Modified Charlson Comorbidity Score \<2 7. Adult Comorbidity Evaluation (ACE)-27 Index \<2 8. Pre-existing peripheral neuropathy ≤1 9. Baseline creatinine clearance \>60ml/min, calculated by Cockcroft-Gault Formula or derived by collection of 24-hour urine. Males: Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine Clearance (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 10. Adequate serum hematological function defined as: * Absolute neutrophil count ≥1.5 × 109/l * Hemoglobin ≥9.0 g/dl * Platelet ≥100 × 109/l 11. Adequate serum biochemical functions defined as: * Alanine transferase ≤3 × upper limit of normal range (ULT) * Aspartate transferase ≤3 × ULT * Total bilirubin ≤2 x ULT * Albumin ≥2.8 g/dl 12. For women of childbearing potential, a negative serum or urine pregnancy test within 14 days prior to the start of treatment for their NPC. Women will be considered postmenopausal if they are amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: * Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). * Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 13. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 14. Body Weight \>30kg 15. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 16. Must have a life expectancy of at least 12 weeks. Exclusion Criteria: 1. Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter. 2. Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study. 3. Has had a prior monoclonal antibody within 4 weeks or 5 half-lives, whichever is shorter, prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4. Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., ≤Grade 1 or at baseline) from adverse events due to a previously administered agent. \*Note: Subjects with permanent ≤Grade 2 toxicities (e.g. neuropathy) or toxicities corrected through routine medical management (e.g. thyroid replacement for hypothyroidism), are an exception to this criterion and may qualify for the study. \*Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. \*Note: Subjects with ≤Grade 2 amylase or lipase elevations abnormalities that have no corresponding clinical manifestations (e.g. manifestation of pancreatitis), are an exception to this criterion and may qualify for the study. 5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy 6. Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis). 7. Has an active infection requiring intravenous systemic therapy or hospital admission. 8. Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 9. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment. 10. Has a known history of Human Immunodeficiency Virus (HIV) (HIV type 1/2 antibodies). Routine checking for Anti-HIV type 1 or Anti-HIV type 2 is not mandatory. 11. Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study. 12. Has received a live vaccine 30 days prior to the first dose of trial treatment. 13. Has experienced Grade 4 toxicity on treatment with prior radiation. 14. Has experienced Grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation, anti programmed cell death-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy. 15. Is taking \> 4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required \> 4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment. 16. Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody. 17. Prior systemic therapy utilizing an anti CTLA-4 or PD-1/PD-L1 agent or other forms of immunotherapy. 18. Has had prior radiation therapy 19. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria 1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. 2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician 20. Major surgical procedure (as defined by the Investigator within 28 days prior to the first dose of IP. Local surgery of isolated lesions for palliative intent is acceptable. 21. History of allogenic organ transplantation. 22. History of leptomeningeal carcinomatosis 23. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). 24. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: 1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) 2. Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent 3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)