Actively Recruiting
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
Led by University of Chicago · Updated on 2025-12-02
36
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
U
University of Chicago
Lead Sponsor
E
Exelixis
Collaborating Sponsor
AI-Summary
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 and/or metastatic squamous cell carcinoma of the head and neck (R/M 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 mg/m2, 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.
CONDITIONS
Brief Title
Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck considered incurable by local therapies
- Primary tumor in oropharynx, oral cavity, hypopharynx, larynx, nasopharynx, sinonasal, or unknown primary
- Age 18 years or older
- ECOG Performance Status of 0 or 1
- Measurable disease by RECIST 1.1 criteria
- HPV (p16) testing required for oropharyngeal cancer
- For previously untreated R/M disease, PD-L1 combined positive score (CPS) of 1 or greater; no PD-L1 restriction if prior anti-PD(L)1 therapy received
- Recovery to baseline or Grade 1 severity from any prior adverse events
- Adequate organ and marrow function including ANC ≥1500/mm3, platelets ≥100,000/mm3, hemoglobin ≥9 g/dL, normal liver and kidney function
- Ability to understand and comply with protocol and provide informed consent
- Sexually active fertile subjects must use highly effective contraception during study and specified periods after last drug doses
You will not qualify if you...
- Prior treatment with Zanzalintinib, Cetuximab, or other VEGFR or EGFR inhibitors
- More than two prior systemic therapy lines in recurrent/metastatic setting
- Disease relapse within 3 months of definitive therapy
- Recent treatment with small molecule kinase inhibitors, chemotherapy, biologics, or anticancer therapies within specified time frames
- Brain metastases or cranial epidural disease unless stable for at least 4 weeks after treatment
- Use of oral anticoagulants or platelet inhibitors unless stable doses of acceptable anticoagulants
- Active infection requiring systemic treatment or serious cardiovascular, gastrointestinal, or other health issues
- Known or suspected autoimmune disease except type I diabetes or controlled skin disorders
- Pregnancy or breastfeeding
- Other malignancies within past 2 years except certain localized or low-grade cancers
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 42-day cycles until disease progression or discontinuation
Participants receive the combination of Zanzalintinib, Pembrolizumab, and Cetuximab in 42-day cycles to determine the optimal dosing and evaluate safety and effectiveness.
Multiple visits on days 1, 15, and 29 of each cycle for drug administration and monitoring
Duration - Up to 2 years from the final participant's last treatment
Participants are monitored for safety, progression-free survival, and overall survival after treatment ends.
Periodic visits for assessments during follow-up period
Trial Site Locations
Total: 1 location
1
University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Actively Recruiting
Research Team
C
Clinical Trials Intake
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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