Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status; Substudy-01

To join this study, you would need to have head and neck squamous cell carcinoma that has been confirmed by a doctor and has either come back or spread, and it's not possible to cure it with local treatments like surgery or radiation. You also shouldn't have received any previous treatment specifically for the cancer that has come back or spread. However, if your cancer came back more than six months after you finished a platinum-based chemotherapy for advanced disease in a specific area, you might still be able to join. You need to have at least one part of your cancer that can be measured using scans like CT or MRI, and suitable tissue samples from your tumour must be available for testing. Your general health, as assessed by doctors using a common scale (ECOG performance status), should be good (score of 0 or 1). If your cancer is in the oropharynx area, the HPV status (p16 test) of your tumour also needs to be known.

Certain conditions would prevent you from joining the study. For example, if you have cancer in the nose and sinus areas (nasopharynx, paranasal sinuses) or salivary glands, or if the original source of your cancer is unknown or it's a skin cancer. If your cancer could still be cured by local treatments, you wouldn't be eligible for this study. Also, if your cancer came back within six months of receiving platinum-based chemotherapy for locally advanced disease, you wouldn't be able to participate. If you have a history of specific lung conditions (like pneumonitis that needed steroids), or an active autoimmune disease that has required treatment in the last two years, you would also be excluded.

If you join this study, you would receive one of the treatment combinations: either two new drugs (domvanalimab and zimberelimab) plus chemotherapy (paclitaxel and carboplatin), or one new drug (zimberelimab) plus chemotherapy. All these medicines are given as infusions directly into your bloodstream. You would have regular visits to the hospital for these infusions, physical examinations, blood tests, and imaging scans (like CT or MRI) to check how the treatment is working and monitor your health. The exact schedule of visits would be explained to you, but it would involve frequent appointments, especially at the beginning of the treatment period. The total duration of your participation would depend on how your body responds to the treatment and if you experience any side effects, but generally, studies like this involve treatment for several months, followed by regular follow-up appointments.