Phase I Trial of Zanzalintinib with Pembrolizumab and Cetuximab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

What this Trial Is About

Researchers are evaluating the safety, tolerability, and optimal dosing of a combination treatment involving Zanzalintinib, Pembrolizumab, and Cetuximab in patients with recurrent andor metastatic squamous cell carcinoma of the head and neck RM HNSCC. This Phase I clinical trial aims to find the highest dose patients can tolerate and recommend a dose for future studies, while also exploring treatment effectiveness measures such as progression-free and overall survival. The study targets a patient group with limited treatment options, focusing on overcoming resistance within the tumor environment. Participants receive these drugs in repeating 42-day cycles. Zanzalintinib is taken daily by mouth at varying doses 20 mg, 40 mg, 60 mg, or the recommended phase 2 dose identified during the study. Cetuximab is given by infusion on days 1, 15, and 29 of each cycle at a dose of 500 mgm2, and Pembrolizumab is administered by infusion on day 1 at 400 mg. The study includes dose escalation groups to determine safety and dosing and an expansion group enrolling after dose levels are established. During the trial, participants are closely monitored for side effects and treatment responses. Assessments include measuring tumor changes using RECIST 1.1 criteria, testing HPV status for oropharyngeal cancers, evaluating immune markers, genetic changes, and circulating tumor DNA levels. Safety and tolerability are tracked throughout treatment, with progression-free survival and overall survival followed for up to two years after the last participant joins. The study lasts approximately 24 months on average per participant, including treatment and follow-up.

Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC