Nivolumab in Children and Adults With Nasopharyngeal Carcinoma

Inclusion Criteria:

1. Histologically confirmed new diagnosis of nasopharyngeal carcinoma according to thecurrent WHO classification in children and adolescents, aged between 3 years and 17years, OR histologically confirmed new diagnosis of EBV-positive nasopharyngealcarcinoma, WHO stage II or III, in subjects ≥ 18 years

2. Stage II or higher in patients ≤ 25 years of age, stage III and IV in patients > 25years of age (AJCC, 8th edition)

3. Measurable disease by MRI per RECIST 1.1 criteria

4. Sufficient tumor tissue to be sent for central review, including PD-L1 staining,either as 1 or 2 full blocks (preferred) or a minimum of 25 slides, obtained fromcore biopsy, punch biopsy, excisional biopsy or surgical specimen

5. Written informed consent by legal guardians (if patient not ≥ 18 years) and patientprior to study participation

Exclusion Criteria:

1. Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II inpatients > 25 years of age

2. Recurrent nasopharyngeal carcinoma

3. Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapyand/or radiotherapy

4. Prior chemotherapy and/or radiotherapy

5. Other active malignancy

6. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, orany other antibody or drug specifically targeting T-cell co-stimulation orcheckpoint pathways.

7. The subject received an investigational drug within 30 days prior to inclusion intothis study

8. Subjects who are enrolled in another clinical trial

9. Subjects with prior organ allograft or allogenic bone marrow transplantation

10. Subjects with an active, known or suspected autoimmune disease. Participants withtype I diabetes mellitus, hypothyroidism only requiring hormone replacement, skindisorders (such as vitiligo, psoriasis, or alopecia) not requiring systemictreatment, or conditions not expected to recur in the absence of an external triggerare permitted to enrol.

11. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before start of therapy. Inhaled or topical steroids, and adrenalreplacement steroid doses > 10 mg daily prednisone equivalent, are permitted in theabsence of active autoimmune disease.

12. Any positive test for hepatitis B virus or hepatitis C virus indicating acute orchronic infection

13. Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS).

14. Inadequate hematologic, renal or hepatic function defined by any of the followingscreening laboratory values:

15. WBC < 2 000/µl

16. Neutrophils < 1 500/µl

17. Platelets < 100 x 10e3/µL

18. Hemoglobin < 9.0 g/dL

19. Creatinine >1.5 x ULN or creatinine clearance < 50 mL/min (using the CockcroftGault formula or Schwartz formula in patients < 18 years)

20. AST/ALT > 3 x ULN (> 5 x ULN if liver metastases)

21. Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome who musthave a total bilirubin level ≥ 3.0 x ULN)

22. Hearing loss > 20 dB loss at 3 kHz due to an inner ear disorder and not caused bytumour burden

23. History of allergy or hypersensitivity to platinum-containing compounds or otherstudy drug components

24. Clinically significant, uncontrolled heart disease (including history of any cardiacarrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conductionabnormality within 12 months of screening).

25. Vaccinated with live attenuated vaccines within 4 weeks of the first dose of thestudy drug.

26. Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lanskyscore ≥ 60 (age < 16).

27. The subject has a history of any other illness, which, in the opinion of theInvestigator, might pose an unacceptable risk by administering study medication.

28. The subject has any current or past medical condition and/or required medication totreat a condition that could affect the evaluation of the study.

29. Pregnant females as determined by positive [serum or urine] hCG test at Screening orprior to dosing. Participants of child-bearing age should use adequate contraceptionas defined in the study protocol. (Please refer to section 4.4)

30. Lactating females

31. Subjects, who are committed to an institution by virtue of an order issued either bythe judicial or the administrative authorities

32. The subject is unwilling or unable to follow the procedures outlined in the protocol

33. The subject is mentally or legally incapacitated.