A Phase Ib Trial of MVA-EBNA1/LMP2 Vaccine in Nasopharyngeal Carcinoma

Inclusion Criteria:

1. Histologically confirmed NPC in which the presence of EBV has been confirmed in the tumour by immunohistochemistry for viral antigens or EBV early RNA (EBER) fluorescent in situ hybridisation (FISH).
2. Patients in remission or with current disease for whom no standard therapy is currently appropriate or required.
3. Patients who have received primary treatment for their malignancy (radiotherapy ± chemotherapy) and up to one additional second-line course of therapy.
4. Life expectancy of at least 6 months.
5. World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1).
6. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient receives their first vaccination with MVA-EBNA1/LMP2.

   Laboratory Test Value required Haemoglobin (Hb) ≥10.0 g/dL, Lymphocyte count ≥0.5 x 10\^9/L after ≥ 6 weeks have elapsed from completion of chemotherapy, Absolute neutrophil count (ANC) ≥1.0 x 10\^9/L, Platelet count ≥ 75 x 10\^9/L, Serum bilirubin ≤1.5 x upper limit of normal (ULN), Alkaline phosphatase (ALP) AND alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) ≤ 2.5 x ULN, Calculated creatinine clearance ≥50 mL/min (uncorrected value)
7. 18 years or over.
8. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up.

Exclusion criteria

1. Radiotherapy, chemotherapy, endocrine therapy, immunotherapy or investigational medicinal products within 6 weeks prior to trial entry.
2. Patients who, in the opinion of the investigator and multidisciplinary team managing the patient, may require another oncological treatment within 14 weeks of the first vaccination.
3. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities, which in the opinion of the Investigator and the Sponsor should not exclude the patient.
4. Current active auto-immune disease requiring therapy.
5. Current active eczema requiring therapy.
6. Allergy to eggs or egg products.
7. History of anaphylaxis or severe allergy to previous vaccinations or medications. Patients with a documented history of allergy to gentamicin should be discussed with the Sponsor prior to trial entry.
8. Previous splenectomy or splenic radiation, or with known splenic dysfunction.
9. Receiving current immunosuppressive medication including systemic use of corticosteroids. Prophylactic use of inhaled steroids is permitted.
10. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the trial and for six months afterwards are considered eligible.
11. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (for example, condom plus spermicidal gel) to prevent exposure to the foetus or neonate.
12. Major thoracic or abdominal surgery from which the patient has not yet recovered.
13. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.
14. Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
15. History of Unstable Angina Pectoris or Myocardial Infarction up to 6 Months prior to trial entry.
16. Any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial.
17. Is a participant or plans to participate in another interventional clinical trial, whilst taking part in this Phase Ib study of MVA-EBNA1/LMP2. Participation in an observational trial would be acceptable.