Evaluation of Follow-up Treatment with Dostarlimab in Adult Patients with Unresectable Head and Neck Squamous Cell Carcinoma (HNSCC)

Head and neck squamous cell carcinoma (HNSCC) refers to various forms of head and neck cancer that arise from mucosal cells in the oral cavity, pharynx, larynx, or nasal cavity. The main risk factors for this disease are smoking, excessive alcohol consumption, and infection with the human papillomavirus (HPV). The tumor often grows aggressively, can spread to lymph nodes at an early stage, and, if left untreated, leads to severe functional impairments in speaking, swallowing, and breathing. Some of these tumors are PD-L1-positive, meaning they express the PD-L1 protein on their surface. This protein suppresses the immune system by blocking T cells. As a result, the cancer cells can evade the immune response and grow unchecked.

The standard treatment for head and neck squamous cell carcinoma depends on the tumor size, location, and resectability. Tumors that cannot be surgically removed (unresectable) are typically treated with platinum-based chemoradiotherapy (RCT). This means that radiation therapy is combined with concurrent chemotherapy to stop or reduce tumor growth. After completion of RCT, there is currently no standard follow-up treatment; instead, close follow-up care is provided. In the event of a relapse or an inadequate response to therapy, a so-called salvage operation—that is, surgical removal of the remaining or regrown tumor—may be considered. If the cancer is no longer curable, palliative immunotherapy with PD-1 or PD-L1 inhibitors is used; these activate the immune system and slow tumor growth to improve quality of life. The drug dostarlimab, which is used in this study, is an antibody against PD-1 receptors and is already approved for the treatment of certain endometrial carcinomas. It has not yet been approved for head and neck squamous cell carcinomas.

The goal of this Phase 3 study is to determine whether follow-up treatment after completion of chemoradiotherapy could provide a survival benefit in patients with unresectable head and neck squamous cell carcinomas. To this end, patients will be randomly assigned to two groups. One group will receive the study drug dostarlimab, while the other will receive a placebo (a drug without an active ingredient) as a control. Both groups will receive the medication as an intravenous infusion. Treatment begins with four infusions every three weeks (q3w) and then switches to seven infusions every six weeks (q6w) over a total period of 54 weeks. Neither the patients nor the medical staff know which drug is being administered (double-blind). As part of the study, information on efficacy and safety will be collected and evaluated over a period of approximately 5 years. The treatment has not yet been approved; the study is experimental.

Women and men aged 18 and older with unresectable, PD-L1-positive head and neck squamous cell carcinoma (HNSCC) who have completed curative cisplatin-based chemoradiotherapy are eligible to participate in the study. Patients who have already received another treatment for the disease (other than chemoradiotherapy) are not eligible to participate in the study.