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)
Authors: Fein Seymour , Guttman Lisa , Marino Mark T. , Fong Yuman 
Published: September 2020

Abstract
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 &lt 2 of 6 patients experience a DLT dose escalation will proceed. Patients with an ongoing objective response will be followed on study by periodic imaging or physical examination at 3 month intervals. Patients will undergo serial sampling of blood and urine and oral and rectal swabs at specified times after each dose for evaluation of viral titers by viral plaque assay (VPA) and PCR. Immunophenotyping and cytokine analysis for immune response will be performed for analysis of lymphocyte subsets and cytokines including interferon gamma, tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1) and interleukin-6 (IL-6). In selected patients, tumor biopsies will be obtained for histological examination and viral titers. hNIS based imaging (SPECT) will be conducted 24 to 96 hours after the first dose. Safety and tolerance will be assessed by physical examination, vital signs, electrocardiogram (ECG), clinical laboratories, ECOG performance status and adverse events.
Results: Pending.
Conclusions: Pending.
Citation Format: Seymour Fein, Lisa Guttman, Mark T. Marino, Yuman Fong. 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) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT243.