EACH: Evaluating Avelumab in Combination With Cetuximab in Head and Neck Cancer

Prior treatment

• Disease suitable for treatment with curative intent.
• Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
• Treatment with any investigational agent within 4 weeks prior to the first dose of trial treatment.
• Anti-cancer monoclonal antibody therapy within 4 weeks prior to randomisation
• Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to randomisation.
• Persisting grade ≥2 toxicity related to prior therapy
• Prior organ transplantation including allogenic stem-cell transplantation
• Has received a live vaccine within 28 days prior to first dose of trial treatment
• Has 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 (n.b. the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC)
• Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent.
• Current use of immunosuppressive medication
• Known prior severe hypersensitivity to either investigational product or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies

Other illness

• Patients with undifferentiated nasopharyngeal or sino-nasal cancers.
• Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial.
• Hepatitis infection at screening
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
• Active infection requiring systemic therapy
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e. bronchiolitis obliterans, cryptogenic organising pneumonia), or evidence of active pneumonitis on screening chest CT scan. (History of radiation pneumonitis in the radiation field is permitted).
• Significant cardiovascular disease
• Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis.
• Patients with a history of keratitis, ulcerative keratitis or severe dry eye.

Lab values

• Any serious and/or unstable pre-existing medical, psychiatric or other condition, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Other

• Women who are pregnant or breast feeding.
• Grade 3 or 4 peripheral neuropathy.
• Patients who are not able to give informed consent for any reason.
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis

• Safety run in: Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma that is considered incurable by local therapies
  • Phase II: Histologically/cytologically confirmed recurrent/metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
• Prior treatment with a platinum agent (either for recurrent/metastatic disease; or as part of radical intent multimodality treatment if disease has recurred within 6 months). (NB: This criterion is not applicable for the safety run-in).
• No previous treatment with cetuximab for metastatic/recurrent disease
• Age ≥18 years
• WHO Performance Status 0 or 1
• Measurable disease according to RECIST v1.1
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• Adequate venous access for administration of treatment and collection blood samples for exploratory biological samples
• Willing to have a new biopsy (NB: This criterion is not applicable for the safety run-in).
• Life expectancy of \>3 months
• Women of child-bearing potential and male patients with partners of child-bearing potential must agree to use adequate contraception methods from date of informed consent, which must be continued for 120 days after completion of trial treatment.
• Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options
• Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits.