Loading clinical trials...

RECRUITINGPHASE1

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

NCT06912087•University of Chicago

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M HNSCC), which is considered incurable by local therapies.
•Primary tumor locations: oropharynx, oral cavity, hypopharynx, larynx, nasopharynx, and sinonasal. Unknown primary is also eligible.
•Age: Participants must be at least 18 years old.
•ECOG Performance Status: Must be 0-1.
•Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
•For oropharyngeal cancer: HPV (p16) testing is required. p16 Immunohistochemistry (IHC) is sufficient for Human Papillomavirus (HPV) testing.
•Programmed cell death ligand 1 (PD-L1) combined positive score (CPS) : For patients with previously untreated R/M disease, a combined positive score (CPS) of 1 or greater is required. There is no PD-L1 restriction for patients who have previously received anti-PD(L)1 therapy.
•Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from any adverse events (AEs), including immune-related AEs from prior treatments.
•Adequate organ and marrow function, including:
•Absolute neutrophil count (ANC) ≥ 1500/mm3.
+5 more criteria

Exclusion Criteria

•Prior treatment with Zanzalintinib or other vascular endothelial growth factor receptor (VEGFR)-targeted therapies, -Cetuximab, or other epidermal growth factor receptor (EGFR) inhibitors.
•More than two prior lines of systemic therapy in the recurrent/metastatic setting.
•Relapsed disease within 3 months of definitive therapy.
•Prior treatment with small molecule kinase inhibitors, chemotherapy, biologic, or other anticancer therapies within certain time frames (2-4 weeks before the first dose of study treatment).
•Brain metastases or cranial epidural disease unless stable after treatment for at least 4 weeks.
•Concomitant anticoagulation with oral anticoagulants or platelet inhibitors, unless on stable doses of acceptable anticoagulants.
•Active infection requiring systemic treatment or significant cardiovascular, gastrointestinal, or other serious health issues that may affect study participation.
•Known or suspected autoimmune disease, except for specific conditions like type I diabetes or controlled skin disorders.
•Pregnancy or breastfeeding: Women must not be pregnant or breastfeeding at screening.
•Other malignancies within the past 2 years (except for certain low-grade cancers like localized skin cancers).

Locations (1)

University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, United States

Key Dates

Start Date

September 29, 2025

Primary Completion Date

June 5, 2027

Completion Date

June 5, 2027

Last Updated

December 2, 2025

Enrollment

ESTIMATED participants

Conditions

Head and Neck NeoplasmsCarcinoma, Squamous CellNeoplasm Recurrence, LocalNeoplasm MetastasisRecurrent Squamous Cell CarcinomaMetastatic Squamous Cell Carcinoma

Interventions

Zanzalintinib

DRUG

Cetuximab

DRUG

Pembrolizumab

DRUG

Contacts

Clinical Trials Intake

CONTACT

1-855-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Circulating Tumor DNA (ctDNA) in Locally Advanced Head and Neck Squamous Cell Carcinoma

NCT04099290

Head and Neck NeoplasmCarcinoma, Squamous Cell

View study

RECRUITINGPHASE3

Head and Neck Cancer Study Project in the Geriatric Population

NCT06998069

Head and Neck Neoplasms

View study

RECRUITING

NIDCD Otolaryngology Clinical Protocol Biospecimen Bank

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: December 2, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Circulating Tumor DNA (ctDNA) in Locally Advanced Head and Neck Squamous Cell Carcinoma

Head and Neck Cancer Study Project in the Geriatric Population

NIDCD Otolaryngology Clinical Protocol Biospecimen Bank

Prospective Observational Study to Validate Circulating HPVDNA and Prognostic Genomic Biomarkers in HPV-associated OPSCC

Iparomlimab and Tuvonralimab With Chemoradiation for the Treatment of Locally Recurrent and Oligometastatic Cervical Cancer

Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients - Pivotal Trial