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

Description

This Phase I, single-site clinical trial investigates the combination therapy of Zanzalintinib, an oral tyrosine kinase inhibitor, with Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, and Cetuximab, an anti-EGFR monoclonal antibody, in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The primary objective is to determine the maximally tolerated dose (MTD) and the recommended Phase II dose (RP2D) of Zanzalintinib in combination with Pembrolizumab and Cetuximab.

Secondary objectives include evaluating safety, tolerability, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives will investigate the effects of the treatment on plasma circulating tumor DNA (ctDNA) levels, immune phenotype, genetic alterations, and histopathologic changes in tumor biopsies.

The trial uses a dose-escalation design, with a 42-day treatment cycle, to assess safety and dose-limiting toxicities. This combination targets the immune-suppressive tumor microenvironment, aiming to overcome resistance mechanisms and improve clinical outcomes for a population with limited therapeutic options.