Phase I Clinical Trial of VTX-2337, a Small Molecule Toll-Like Receptor 8 (TLR8) Agonist in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinomas of the Head and Neck (SCCHN)
I. To determine the safety, tolerability and to assess the dose-limiting toxicities (DLT) of
VTX-2337 (TLR8 Agonist VTX-2337) when given in conjunction with cetuximab in order to define
the maximum tolerated dose (MTD)/recommended phase II dose (RP2D).
I. To determine the pharmacodynamic immune response to VTX-2337 in combination with
II. Correlative assessments of immunologic response and activity will be performed,
including: Quantitative evaluation of baseline immune status via in-vitro assessment of
cytokine and chemokine response to immunostimulatory agents; quantitative assessment of
plasma cytokines, chemokines, and other inflammatory markers via protein array; quantitative
assessment of natural killer (NK) cells via flow cytometry; quantitative assessment of
antigen-specific responses in cytokine-producing cells to common prognostic SCCHN antigens
via interferon (INF)gamma-enzyme-linked immunosorbent spot (ELISpot).
III. To assess whether subjects with functional genetic variations in the TLR8 and
FC-gamma-R IIIA genes have altered biological and/or clinical responses to VTX-2337, genetic
characterization of subjects will be performed via standard genotyping assays.
I. To assess preliminary evidence of anti-tumor activity for the combination of VTX-2337 and
cetuximab, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
OUTLINE: This is a dose-escalation study of TLR8 Agonist VTX-2337.
Patients receive cetuximab intravenously (IV) over 60-120 minutes on days -28, -21, -14, -7
of weeks -4 to -1. Patients then receive cetuximab IV on days 1, 8, 15, and 22 and TLR8
agonist VTX-2337 subcutaneously (SC) on days 1, 8, 15. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose and the toxicities of TLR8 agonist VTX-2337 in combination with cetuximab
Frequency and severity of hematologic and non-hematologic adverse events will be compiled for each dose cohort. Assessment of adverse events will include type, incidence, severity (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0), duration, seriousness, and relatedness; and clinically significant laboratory abnormalities.
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
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