This is a phase II, open-label study to assess the efficacy of monalizumab and cetuximab in terms of molecular residual disease (MRD) clearance and treatment outcome in patients with MRD after definitive treatment for high risk locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). MRD is defined as ctDNA detection in plasma after definitive treatment. Approximately 200 patients are expected to be enrolled.~The study is divided in 5 parts:~Part A and Part B are common for all patients in the study, which are defined as the periods of definitive treatment and post definitive treatment. Definitive treatment will be either surgery followed by radiation or chemoradiation; definitive radiation or definitive chemoradiation according to standard of care (SOC) in our institution. A baseline ctDNA sample collection and CT staging will be done before treatment. ctDNA analysis will be performed in Part B at approximately week 5 and at week 10 of this period, and patients will be classified as MRD positive or MRD negative at the end of this part.~Part C is the randomized and interventional part of the study (n=60) for patients with MRD. The patient will be randomized 3:1 to Arm A (treatment with monalizumab 750 mg IV Q2W and cetuximab 500 mg/m2 IV Q2W) or Arm B (observation). Patients in Arm A will continue treatment until the occurrence of any of these circumstances: after completion of 8 cycles, intolerable toxicity or patient decision. ctDNA analysis will be done at week 9 of Part C.~Part D is the follow up part for patients with MRD. Two ctDNA samples will be analyzed at week 2 and at week 10 of Part D. A final sample will be also collected if the patient has radiological or clinical progression. A CT/MRI scan will be performed at week 2 of Part D and, if clinically needed, according to SOC.~Part E is the observational follow up part for patients without MRD. A ctDNA sample will be collected at radiological or clinical progression.
This is a phase II, open-label study to assess the efficacy of monalizumab and cetuximab in terms of molecular residual disease (MRD) clearance and treatment outcome in patients with MRD after definitive treatment for high risk locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). MRD is defined as ctDNA detection in plasma after definitive treatment. Approximately 200 patients are expected to be enrolled.