Clinical trial NCT02938273 (phase 1, status: completed)
Conditions: carcinoma, squamous cell of head and neck
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: avelumab, cetuximab
SMILES: NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1, [H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O
Eligibility criteria:

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent for the trial.

          -  Be ≥18 years of age on day of signing informed consent.

          -  WHO Performance Status 0,1 or 2

          -  Have histologically confirmed Locally Advanced (i.e. stage III or IV) head and neck
             squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx.

          -  Unfit for concurrent chemoradiation with cisplatin, e.g. GFR < 60 ml/min,
             cardiovascular co-morbidity, hearing loss or polyneuropathy or written refusal for
             treatment with chemotherapy

          -  Be willing to provide tissue for tumor microenvironment analysis from archival tumor
             material (i.e. formalin fixed, paraffin embedded (FFPE) tumor tissue block not older
             than 42 days before start of treatment) or newly obtained core or excisional biopsy,
             and willingness to provide a core or excisional biopsy at day 14 (±2 days) after start
             of treatment.

          -  Have at least one measurable lesion as defined by RECIST 1.1.

          -  Be willing and able to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

          -  Demonstrate adequate organ function, i.e. adequate bone marrow function, including:

               1. Absolute Neutrophil Count (ANC) ≥1.5 x 109/L;

               2. Platelets ≥100 x 109/L;

               3. Hemoglobin ≥6 mmol/L. Adequate renal function, i.e. estimated creatinine
                  clearance ≥30 mL/min as calculated using the Cockcroft-Gault (CG) equation (or
                  local institutional standard method).

        Adequate liver function, including:

          1. Total serum bilirubin ≤1.5 x ULN;

          2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or AST
             and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the
             liver).

               -  Have a negative serum pregnancy test at screening (for females of childbearing
                  potential).

               -  Both male and female subjects should agree to use highly effective contraception
                  if the risk of conception exists. (Note: The effects of the trial drug on the
                  developing human fetus are unknown; thus, women of childbearing potential and men
                  able to father a child must agree to use 2 highly effective contraception,
                  defined as methods with a failure rate of less than 1 % per year.) Highly
                  effective contraception is required throughout the study and for at least 120
                  days after Avelumab treatment.

        Exclusion Criteria:

        - Prior treatment with: Systemic therapy, radiotherapy or surgery directed at locally
        advanced SCCHN. Immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2,
        anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody
        (including ipilimumab), or any other antibody or drug specifically targeting T-cell
        co-stimulation or immune checkpoint pathways.

          -  A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Current or prior use of immunosuppressive medication within 7 days prior to
             registration, except the following:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g.
                  intra-articular injection);

               -  Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or
                  equivalent;

               -  Steroids as premedication for hypersensitivity reactions (eg, CT scan
                  premedication).

          -  Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any
             history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially
             controlled asthma Global Initiative for Asthma 2011.

          -  Known prior or suspected hypersensitivity to study drugs or any component in their
             formulations.

          -  Diagnosis of any other malignancy within 5 years prior to start of treatment except
             for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
             of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on
             surveillance with no plans for treatment intervention (e.g. surgery, radiation, or
             castration).

          -  Significant acute or chronic infections including, among others:

               -  Known history of testing positive test for human immunodeficiency virus (HIV) or
                  known acquired immunodeficiency syndrome (AIDS)

               -  Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV
                  antibody tested positive)

          -  Prior organ transplantation, including allogeneic stem cell transplantation

          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent, except the following:

               1. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease
                  not requiring immunosuppressive treatment

               2. Subjects requiring hormone replacement with corticosteroids if the steroids are
                  administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or
                  10 mg equivalent prednisone per day

               3. Administration of steroids through a route known to result in a minimal systemic
                  exposure (topical, intranasal, intro-ocular, or inhalation)

          -  Persisting toxicity related to prior therapy of Grade >1; however, alopecia and
             sensory neuropathy Grade ≤ 2 is acceptable

          -  Pregnancy or lactation

          -  Known alcohol or drug abuse

          -  All other significant diseases (for example, inflammatory bowel disease, uncontrolled
             asthma), which, in the opinion of the Investigator, might impair the subject's
             tolerance of trial treatment

          -  Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines (for example, inactivated
             influenza vaccines).

          -  Any of the following in the previous 6 months: myocardial infarction, severe/unstable
             angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
             cerebrovascular accident, transient ischemic attack, deep vein thrombosis or
             symptomatic pulmonary embolism.

          -  Subjects with brain metastases