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).
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.
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).
Sequential
Zanzalintinib
DrugExperimental receptor tyrosine kinases (RTKs)
Cetuximab
DrugFood and Drug Administration (FDA) approved monoclonal antibody directed against the epidermal growth factor (EGFR).
Pembrolizumab
DrugFDA approved monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1)
Maximally Tolerated Dose (MTD) of Zanzalintinib in Combination with Pembrolizumab and Cetuximab
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 Cetuximab
The RP2D will be defined as the MTD identified after enrollment to all cohorts.
Progression-Free Survival (PFS)
The secondary outcome measure of Progression-Free Survival (PFS) will assess the time from the first dose of the study drug (Zanzalintinib, Pembrolizumab, and Cetuximab) to the date of documented disease progression (PD) based on RECIST v1.1 or death, whichever occurs first. This measure will help evaluate the efficacy of the combination therapy in delaying disease progression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Overall Survival (OS)
The secondary outcome measure of Overall Survival (OS) will evaluate the time from the first dose of the study drug (Zanzalintinib, Pembrolizumab, and Cetuximab) to the date of death from any cause. This outcome will help assess the overall impact of the combination therapy on patient survival in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Safety of zanzalintinib in combination with pembrolizumab and cetuximab
Adverse events (AEs) leading to discontinuation or death, and severity of AEs will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Click on the lead sponsor to view all of their trials.
University of Chicago
Lead sponsor
Exelixis
Collaborator
