Phase Ib Trial of the Toll-like Receptor 8 Agonist, Motolimod (VTX-2337), Combined with Cetuximab in Patients with Recurrent or Metastatic SCCHN.

摘要: Purpose: As Toll-like receptors (TLR) are key mediators of immune responses, TLR agonists may be important for augmenting the efficacy therapies squamous cell carcinoma head and neck (SCCHN). Motolimod (VTX-2337), a selective small-molecule agonist TLR8, stimulates natural killer (NK) cells, dendritic monocytes. A phase Ib clinical trial assessed safety antitumor activity motolimod in combination with cetuximab patients SCCHN. Correlative biomarkers were explored. Experimental Design: Thirteen recurrent or metastatic SCCHN enrolled this open-label, dose–escalation study using standard 3 + design. Doses (2.5, 3.0, 3.5 mg/m2) given on days 1, 8, 15, fixed weekly doses 28-day cycles. Results: There no protocol-defined dose-limiting toxicities, drug-related deaths, evidence synergistic toxicities between cetuximab. Clinical tolerability at mg/m2 dose level was not optimal repeated dosing 3.0 identified as MTD. Two achieved partial responses an overall response rate 15%. Five had disease stabilization equating to control 54%. Statistically significant increases plasma cytokines frequency activation circulating NK cells observed. Conclusions: can safely administered acceptable toxicity profile. Encouraging robust pharmacodynamic is being further investigated II (ClinicalTrials.gov ID: NCT01836029). Clin Cancer Res; 23(10); 2442–50. ©2016 AACR.