A single-arm phase II study of cetuximab plus platinum and taxane-based chemotherapy followed by AVElumab and Cetuximab as first-line therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients with PD-L1 combined positive score (CPS)≥1≤19: the immunotherapy sequence reversal

PI: Dott. Salvatore Alfieri 

The AVEC-119 study proposes the combination of Cetuximab plus platinum- and taxane-based chemotherapy for 3 cycles, followed by maintenance therapy with Avelumab immunotherapy and Cetuximab targeted therapy, as a first-line treatment in patients with locally recurrent and/or metastatic squamous cell carcinoma of the head and neck that is PD-L1 (Programmed Death-Ligand 1) positive. 

This study, conducted in accordance with European regulations, is considered experimental, as the combination of the study drugs has not yet been approved by health authorities for this cancer type. 

The rationale of the study is based on the fact that Cetuximab and taxane agents, within polychemotherapy regimens, may synergistically cooperate through their immunostimulatory effects, thereby enhancing the immune response. 

The objective of the study is to propose a treatment regimen aimed at improving overall survival for patients, as well as increasing antitumor responses in this specific phase of the disease. 

Specifically, the antitumor activity is expressed as follows: 

• Cetuximab is a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR), resulting in inhibition of tumor cell proliferation, stimulation of tumor cell death, and prevention of metastasis formation. 
• Paclitaxel and Platinum agents (Cisplatin or Carboplatin) are well-known chemotherapeutic agents with antineoplastic activity. 
• Avelumab is a monoclonal antibody that binds to the PD-L1 ligand of the PD-1 (Programmed Death-1) protein, thereby restoring the immune system's antitumor response through the activation of T lymphocytes and Natural Killer (NK) cells, which can induce the death of cancer cells. 

The study proposes the combination of Cetuximab (administered via weekly intravenous infusion) with Paclitaxel and Platinum (intravenous infusion every 21 days) for 3 cycles, followed by the combination schedule of Avelumab + Cetuximab (intravenous infusions every 15 days) as maintenance therapy. 

The feasibility of patient enrollment in the study will depend on: patient characteristics (demographics, oncological history, and comorbidities), laboratory tests, and radiological parameters, which will be assessed through specific screening examinations before the start of treatment. These assessments will follow well-defined timelines. 

Treatment will continue until maximum response is achieved and will be discontinued only in the event of: 

• disease progression 
• unacceptable toxicity 
• or, as always in clinical trials, a decision by the patient (who will continue to have access to medical care and will not waive any legal rights or entitled benefits) or by the investigator. 

The treatment may also induce adverse events, most of which are known and manageable, for which the investigators will adopt strategies to reduce their severity (e.g., dose reductions or treatment pauses) and to relieve symptoms (by offering symptomatic therapies). 

The study team remains available for more detailed information (email: amo@istitutotumori.mi.it).