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

Launched by UNIVERSITY OF CHICAGO · Mar 28, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, a type of cancer that has come back or spread and cannot be treated with standard local therapies. The study is looking at a combination of three drugs: Zanzalintinib, Pembrolizumab, and Cetuximab. The main goals are to determine the safest dose of Zanzalintinib when given with the other medications and to see how well this combination can help control the cancer and improve survival.

To participate in this trial, patients must be at least 18 years old and have a confirmed diagnosis of recurrent or metastatic squamous cell carcinoma of the head and neck. They should also be in good overall health, with certain measurable disease requirements. Patients who have previously received specific cancer treatments or have certain health conditions might not be eligible. Those who join the trial can expect close monitoring and support throughout the study, and they will need to comply with certain health and safety guidelines. This trial is not yet recruiting participants, but it offers hope for new treatment options for those dealing with this challenging condition.

Gender

ALL

Eligibility criteria

• 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.
• • 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 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).