Study to Assess the Efficacy and Safety of Nivolumab in Combination With Paclitaxel in Subjects With Head and Neck Cancer Unable for Cisplatin-based Chemotherapy (NIVOTAX)

Inclusion Criteria

• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care.
• Histologically confirmed HNSCC (oral cavity, oropharynx, hypopharynx, larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
• Patients not previously treated for recurrent/metastatic disease.
• Radiographically measurable disease as defined by RECIST version 1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression according to RECIST version 1.1.
• Patients unable for cisplatin-based chemotherapy, defined "unable" by:
• Karnofsky 70% or
• Karnofsky 80-100% and amenable to chemotherapy, but:

i. Impaired renal function, creatinine clearance >30 mL/min and 4 weeks prior to inclusion.

• Documentation of PD-L1 status by IHC performed by the central lab at randomization. A pre-treatment tumor tissue sample should be sent. A newly obtained biopsy (within 6 months prior to start of study treatment) is preferred but an archival sample is acceptable, if several tumor samples are available, testing should be performed on the most recently obtained tumor sample.
• Documentation of HPV p16 status (OPC) is required for HNSCC tumor of the oropharynx. For subjects with oropharyngeal cancer, sites are defined in annex 8. HPV status of tumor tissue has to be locally determined at screening by any of the following methods: p16 IHC, in situ hybridization, or polymerase chain reaction based assay. If HPV status by p16 IHC is positive result confirmation by PCR is mandatory.

Exclusion Criteria

• Male or female patients aged 30 mL/min and 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
• History of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function.
• Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents or inhibitors of checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells are prohibited.
• Any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Life-threatening illness unrelated to cancer.
• Female patients who are lactating and breast-feeding or a positive serum pregnancy test during the screening period.
• Systemic anticancer treatment or radiotherapy less than 4 weeks or 5 half-lives, whichever is longer, before the first dose of study treatment or not recovered from acute toxic effects from prior chemotherapy and radiotherapy.
• Prior treatment with investigational agents ≤21 days (≤4 weeks for monoclonal antibodies with evidence of PD) or ≤5 their half-lives (whichever is shorter) before the first dose of study treatment. A minimum of 10 days should elapse from prior therapy to initiating protocol therapy.
• Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
• Systemic infection requiring IV antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
• Known human immunodeficiency virus (HIV) positive (testing not required), or known acquired immunodeficiency syndrome (AIDS).
• Patients with positive test for hepatitis B virus or hepatitis C virus indicating presence of virus, eg, Hepatitis B surface antigen (HBsAg) positive, or Hepatitis C antibody (anti