A Phase III Trial Evaluating Chemotherapy and Immunotherapy for Advanced Nasopharyngeal Carcinoma (NPC) Patients

Key Inclusion Criteria

1. Metastatic or locally recurrent EBV-positive, non-keratinizing and/ or undifferentiated NPC\* who do not have curative options such as chemo-radiation or surgery

   \*Subjects will be enrolled based on confirmed histology diagnosis of the NPC
2. Radiologically measurable disease as per RECIST 1.1
3. Human Immunodeficiency Virus (HIV) negative\*

   \* Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests available within 4 weeks of screening
4. Bilirubin \<2 x upper limit of normal (ULN) and aspartate aminotransferase (AST), alanine aminotransferase (ALT) \<3 x ULN
5. Calculated creatinine clearance (CRCL) ≥40 mL/min. Glomerular Filtration Rate (GFR) is calculated based on Cockcroft-Gault method.
6. Normal corrected calcium levels
7. Absolute neutrophil count \>1200/mm3, hemoglobin (Hb) ≥10 g/dL and platelets ≥100,000/mm3
8. Male or female
9. Age ≥ 18 years or according to local legal age of consent
10. Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) ≤2
11. Written informed consent
12. Life expectancy \>6 months

Key Exclusion Criteria

1. Severe concomitant illness i.e. chronic obstructive pulmonary disease (COPD), ischemic heart disease (IHD), active congestive cardiac failure (CCF), active angina pectoris, uncontrolled arrhythmia, uncontrolled hypertension
2. HIV Positive\*

   \* Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests available within 4 weeks of screening
3. Pregnant or lactating females
4. Refuse of use of contraception during trial (both male and female patients)
5. Investigational therapy less than one month prior to study entry
6. Pre-existing peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] ≥2)
7. Central nervous system metastasis
8. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis and T1\] or any cancer curatively treated \>3 years prior to study entry
9. Positive hepatitis B surface antigen (HBsAg) results
10. Known history of hepatitis C and recovery status has not been determined at time of screening
11. Prior anti-cancer treatment for metastatic or locally recurrent disease, EXCEPT:

    For metastatic or locally recurrent disease, localised palliative radiotherapy is allowed.

    For locally recurrent disease, the following treatment is allowed
    * Prior radiotherapy with curative intent
    * Prior chemo-radiotherapy with curative intent
    * Adjuvant chemotherapy
    * Localised palliative radiotherapy Prior chemotherapy must be \> 6 months before screening
12. Severe intercurrent infections
13. Prior immunotherapy for metastatic or locally recurrent disease

The following is allowable:

• Adjuvant immunotherapy/ biologics Prior adjuvant immunotherapy/ biologics must be \> 6 months before screening