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

330 patients will be randomized after their eligibility status has been fully determined and
informed consent has been obtained. Patients will be randomly allocated to receive either Arm
A (Gemcitabine and Carboplatin (GC) x 4 cycles and EBV-specific CTL) or Arm B (GC x 6 cycles
alone) in a 1:1 ratio using a stratified block randomization scheme. The stratification
variables are country and disease stage (metastatic vs locally recurrent)

After randomization, patients in Arm A will have their peripheral blood taken for the
establishment of cytotoxic T cell line and EBV transformed lymphoblastoid cell line (CTL).
Within two weeks of enrollment, patients will commence combination GC chemotherapy for a
total of 4 cycles. Patients in Stage 2 of study will receive the EBV-specific CTL
immunotherapy.

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

3. Human Immunodeficiency Virus (HIV) negative*

* Status of HIV must be confirmed via a HIV antibody test or other confirmatory tests
available within 12 months before screening or at 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 ≥21 years

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 12 months before screening or at 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 chemotherapy for metastatic or locally recurrent disease

Exceptions:

- 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

Exception:

• Adjuvant immunotherapy/ biologics