Nivolumab in combination with cisplatin and 5-fluorouracil as induction therapy in children and adults with EBV-positive 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 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
• Subjects with prior organ allograft or allogenic bone marrow transplantation

Other illness

• 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
• Nasopharyngeal carcinoma diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
• Other active malignancy
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
• 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

Lab values

• 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

Age

• Newly diagnosed nasopharyngeal carcinoma, Stage I in all patients, Stage II in patients > 25 years of age
• Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Inadequate hematologic, renal or hepatic function
  • Hearing loss > 20 dB loss at 3 kHz
  • 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)
  • Vaccinated with live attenuated vaccines within 4 weeks of the first dose of the study drug
  • Adequate performance status (Karnofsky score ≥ 60 for patients (age ≥ 16), Lansky score ≥ 60 (age < 16)

Other

• Recurrent nasopharyngeal carcinoma
• Lactating females
• The subject is unwilling or unable to follow the procedures outlined in the protocol
• The subject is mentally or legally incapacitated
• Subjects who are enrolled in another clinical trial

• Histologically confirmed new diagnosis of nasopharyngeal carcinoma according to the current WHO classification in children and adolescents aged between 3 and 17 years
• Alternatively to (1): 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
• Written informed consent by legal guardians (if patient not ≥ 18 years) and patient prior to study participation
• Sufficient tumor tissue to be sent for central review, including PD-L1 staining, either as 2 full blocks or a minimum of 25 slides, obtained from core biopsy, punch biopsy, excisional biopsy or surgical specimen