Nivolumab in Children and Adults With Nasopharyngeal Carcinoma

Prior treatment

• Prior chemotherapy and/or radiotherapy
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• The subject received an investigational drug within 30 days prior to inclusion into this study
• Subjects with prior organ allograft or allogenic bone marrow transplantation
• 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 adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug.

Other illness

• Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
• Other active malignancy
• Subjects with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Hearing loss \> 20 dB loss at 3 kHz due to an inner ear disorder and not caused by tumour burden
• History of allergy or hypersensitivity to platinum-containing compounds or other study drug components
• Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening).
• The subject has a history of any other illness, which, in the opinion of the Investigator, might pose an unacceptable risk by administering study medication.
• The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study.

Lab values

• Inadequate hematologic, renal or hepatic function defined by any of the following screening laboratory values:
  • WBC \< 2 000/µl
  • Neutrophils \< 1 500/µl
  • Platelets \< 100 x 10e3/µL
  • Hemoglobin \< 9.0 g/dL
  • Creatinine \>1.5 x ULN or creatinine clearance \< 50 mL/min (using the Cockcroft Gault formula or Schwartz formula in patients \< 18 years)
  • AST/ALT \> 3 x ULN (\> 5 x ULN if liver metastases)
  • Total Bilirubin \> 1.5 x ULN (except subjects with Gilbert Syndrome who must have a total bilirubin level ≥ 3.0 x ULN)
• Pregnant females as determined by positive \[serum or urine\] hCG test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol. (Please refer to section 4.4)

Age

• Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II in patients \> 25 years of age
• Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lansky score ≥ 60 (age \< 16).

Other

• Recurrent nasopharyngeal carcinoma
• Subjects who are enrolled in another clinical trial
• Lactating females
• Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
• The subject is unwilling or unable to follow the procedures outlined in the protocol
• The subject is mentally or legally incapacitated.

• Histologically confirmed new diagnosis of nasopharyngeal carcinoma according to the current WHO classification in children and adolescents, aged between 3 years and 17 years, OR histologically confirmed new diagnosis of EBV-positive nasopharyngeal carcinoma, WHO stage II or III, in subjects ≥ 18 years
• Stage II or higher in patients ≤ 25 years of age, stage III and IV in patients \> 25 years of age (AJCC, 8th edition)
• Measurable disease by MRI per RECIST 1.1 criteria
• 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 from core biopsy, punch biopsy, excisional biopsy or surgical specimen
• Written informed consent by legal guardians (if patient not ≥ 18 years) and patient prior to study participation