Abstract CT243: A first-in-human phase 1 ascending, multiple dose, safety and tolerance study of Vaxinia (CF33-hNIS), a novel chimeric oncolytic poxvirus, administered intratumorally or intravenously in adult patients with mixed advanced solid tumors (MAST)

Introduction and Objective: CF33-hNIS is a novel, chimeric orthopoxvirus with robust anti-tumor activity at relatively low titers and with a low multiple of infectivity (MOI) in a variety of pre-clinical models. This is a Phase 1, open-label, dose escalation study in adult patients with selected advanced or metastatic solid tumors to evaluate the safety and tolerance of CF33-hNIS administered intratumorally (IT) or intravenously (IV). Secondary objectives include assessment of immune activation, tumor infectivity, viral kinetics, anti-tumor activity and identification of a RP2D. Methods: This is a Phase 1, open-label, dose escalation study in sequential cohorts of 3 to 6. Patients with advanced or metastatic melanoma and triple negative breast cancer (TNBC) with superficial lesions accessible for injection will receive IT dosing. Patients with metastatic melanoma, TNBC, urothelial cancer and non-small cell lung cancer (NSCLC) in organs or deep tissues will receive IV infusions of CF33-hNIS. Dose escalation will occur separately for IT and IV dosing. Successive cohorts of 3 patients will be enrolled at each dose level starting with 105 and ascending to 106, 107, 108 and 109 PFU for IT and IV routes. Treatment is given on days 1 and 8 of cycle 1 and day 1 of cycles 2 through 6 every 21 days. Dose escalation will occur if no DLTs are observed among the first 3 patients in a cohort. If 1 DLT occurs, 3 additional patients will be enrolled at that dose. If l 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT243.