Targeted Therapy and Immunotherapy Following Radiation and Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Squamous cell carcinomas of the head and neck (HNSCC) are malignant tumors that develop in the mucous membranes of the mouth, pharynx, and larynx. Common risk factors include smoking, alcohol consumption, and infection with human papillomavirus (HPV). The standard treatment for locally advanced HNSCC is chemoradiotherapy, which combines high-dose radiation therapy with concurrent cisplatin-based chemotherapy, and is considered a potentially curative treatment. Nevertheless, many patients may experience a relapse.

The goal of this Phase 2 study is to evaluate the combination of pembrolizumab and lenvatinib compared to pembrolizumab alone as maintenance therapy following chemoradiotherapy. Pembrolizumab prevents cancer cells from suppressing the body’s immune defense by targeting the PD-L1 protein. Lenvatinib inhibits the tumor’s blood supply and tumor growth. When combined, the two drugs can enhance each other’s effects, thereby improving the overall efficacy of cancer treatment. Pembrolizumab is already approved as a monotherapy for the treatment of HNSCC. The combination of lenvatinib and pembrolizumab is already approved for other types of tumors, but not yet for HNSCC. As part of the study, patients will be randomly assigned to two groups. Group 1 will receive pembrolizumab in combination with lenvatinib, and Group 2 will receive pembrolizumab as monotherapy. Pembrolizumab is administered every three weeks as an infusion through a venous line (intravenously), while lenvatinib is taken daily as a tablet. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Treatment lasts up to twelve months, followed by a follow-up period of up to two years. The primary endpoint of the study is the event-free survival (EFS) rate at two years. The goal of the study is to increase the 2-year survival rate of patients from 60% to 80%. In addition, the study aims to assess the control of cancer growth in the affected area of the body and the safety of the therapy.

Adults aged 18 and older with a head and neck cancer (HNSCC)—for example, in the oral cavity, pharynx, or larynx—are eligible to participate. The tumor must be PD-L1-positive (CPS ≥ 1), and patients must have successfully completed chemoradiotherapy prior to study enrollment without any signs of disease progression. In addition, tumor tissue samples—for example, in the form of FFPE material—must be available. Patients who have already undergone radical surgery or have already received chemotherapy or immunotherapy are excluded from participation. The presence of distant metastases—meaning the cancer has already spread beyond the head and neck region—or other cancers currently requiring treatment also leads to exclusion.