Back to search results

Phase 1 Study of Zanzalintinib with Pembrolizumab and Cetuximab for Head and Neck Cancer

This study is testing a new combination of three drugs for people with recurrent or metastatic (spread to other parts of the body) squamous cell carcinoma of the head and neck (HNSCC). The drugs are Zanzalintinib, Pembrolizumab, and Cetuximab. Zanzalintinib is an experimental drug that targets certain proteins in cancer cells. Pembrolizumab and Cetuximab are FDA-approved drugs that work by boosting your immune system and blocking cancer cell growth. This Phase 1 study aims to find the safest and most effective dose of Zanzalintinib when given with Pembrolizumab and Cetuximab. Researchers will also look at how well the treatment works to shrink tumors and how long people live. You may be eligible if you are at least 18 years old and have HNSCC that has come back or spread and cannot be cured by other treatments. The study plans to enroll 36 participants.

Study design
This is a Phase 1 interventional study, meaning it tests a new treatment in a small group of people. It uses a dose-escalation design to find the best dose of the drugs.
What's involved
The study involves a 42-day treatment cycle to assess safety and side effects. Specific details about visits or procedures are not provided.
Compensation
Not stated in the trial record.
Follow-up
The primary endpoints for this study are measured at the end of the DLT (dose-limiting toxicity) evaluation period (first 28 days of treatment) and at the end of enrollment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06912087

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

Recruiting
PHASE1Ages 18+InterventionalTreatment
University of Chicago
~36 participants
Updated 2025-12-02 on ClinicalTrials.gov
What's tested:ZanzalintinibCetuximabPembrolizumab

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximally Tolerated Dose (MTD) of Zanzalintinib in Combination with Pembrolizumab and Cetuximab
Measured over end of DLT evaluation period (first 28 days of treatment)
+1 more outcome measured

Conditions

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

Explore related trials

Head and Neck Squamous Cell CarcinomaHPVProgrammed Cell Death 1 Ligand 1

Where it's being run

1 sites across 1 states
Illinois1

Study leadership

  • Ari Rosenberg, MD · PRINCIPAL_INVESTIGATOR · University of Chicago Medicine Comprehensive Cancer Center

Who to contact

Clinical Trials Intake
[email protected]
1-855-702-8222
Email the study team

Opens a ready-to-send draft in your own email app — review before sending.

Do you actually qualify for this trial?

Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.

Check eligibility for this trial ~2 min · HIPAA-protected · delete anytime
Eligibility criteria

Inclusion

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.
Platelets ≥ 100,000/mm3.
Hemoglobin ≥ 9 g/dL.
Normal liver and kidney function.
Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
Contraception: Sexually active fertile subjects must agree to use a highly effective method of contraception during the study and for 2 months after the last dose of cetuximab and 4 months after the last dose of pembrolizumab.

Exclusion

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).

What this trial measures

  • Maximally Tolerated Dose (MTD) of Zanzalintinib in Combination with Pembrolizumab and Cetuximabend of DLT evaluation period (first 28 days of treatment)

    The MTD will be defined as the dose combination with a dose-limiting toxicities (DLT) rate closest to the target DLT rate of 25%.

  • Recommended Phase II Dose (RP2D) of Zanzalintinib in Combination with Pembrolizumab and CetuximabEnd of enrollment

    The RP2D will be defined as the MTD identified after enrollment to all cohorts.