NCT06912087

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

A Phase I Study of Zanzalintinib With Pembrolizumab and Cetuximab in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase I clinical trial evaluates the safety, tolerability, and optimal dosing of Zanzalintinib in combination with Pembrolizumab and Cetuximab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The study aims to establish the maximally tolerated dose (MTD) and recommended Phase II dose (RP2D) while also exploring efficacy outcomes, including progression-free survival (PFS) and overall survival (OS).

Detailed 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.

Conditions

• Head and Neck Neoplasms
• Carcinoma, Squamous Cell
• Neoplasm Recurrence, Local
• Neoplasm Metastasis
• Recurrent Squamous Cell Carcinoma
• Metastatic Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Zanzalintinib	Experimental receptor tyrosine kinases (RTKs)
DRUG	Cetuximab	Food and Drug Administration (FDA) approved monoclonal antibody directed against the epidermal growth factor (EGFR).
DRUG	Pembrolizumab	FDA approved monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1)

Timeline

• Start date: 2025-09-29
• Primary completion: 2027-06-05
• Completion: 2027-06-05
• First posted: 2025-04-04
• Last updated: 2025-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study