Status:
RECRUITING
Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC
Lead Sponsor:
University of Chicago
Collaborating Sponsors:
Exelixis
Conditions:
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 squamou...
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 Cetu...
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).
Key Trial Info
Start Date :
September 29 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 5 2027
Estimated Enrollment :
36 Patients enrolled
Trial Details
Trial ID
NCT06912087
Start Date
September 29 2025
End Date
June 5 2027
Last Update
December 2 2025
Active Locations (1)
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1
University of Chicago Medicine Comprehensive Cancer Center
Chicago, Illinois, United States, 60637