Phase I clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 with green fluorescent protein imaging.
Session type: Poster / e-Poster / Silent Theatre session
GL-ONC1 is a genetically engineered vaccinia virus attenuated by insertion of the RUC-GFP (Renilla luciferase and Aequorea green fluorescent protein fusion gene), beta-galactosidase (lacZ) and beta-glucuronidase (gusA) genes into the F14.5L, J2R (thymidine kinase) and A56R (hemagglutinin) loci, respectively. A phase I clinical trial ofIV GL-ONC1 was pursued to evaluate safety, tolerability, tumour delivery, neutralizing antibody development andactivity.
Advanced solid tumours received escalating doses of GL-ONC1 (1×105, 1×106, 1×107, 1×108, 1×109, 3×109 plaque-forming units (pfu) on day 1; 1.667×107 and 1.667×108 pfu on day 1-3; 1×109 pfu on day 1-5 of a 28-day cycle) using a 3+3 dose escalation design. Green fluorescent protein (GFP) imaging was performed on superficial and mucosal tumour lesions at baseline and after each cycle, and on GL-ONC1-related skin rashes.
To date, 24 patients (18 males, median age 60 years) have been treated. One of 6 patients at 1x109 pfu dose level developed a dose-limiting grade 3 rise in AST levels after one infusion. Other commonly reported AEs (grade 1/2) included pyrexia (n=12), musculoskeletal pain (n=7), fatigue (n=7), nausea (n=5), and vomiting (n=4). One patient developed a left common femoral artery embolism of uncertain causality (grade 3). Two patients developed skin rash during the first week of treatment, which appeared green by GFP imaging and were positive to viral plaque assay (VPA). The rash resolved by the end of cycle 1. VPA of blood, urine, stool and sputum were viral sheddinng negative in all but one who had positive for 11 days. Increased neutralizing antibody titres were detected in all tested patients apart from one. Best response by RECIST was stable disease at 24 weeks (n=4) and 8-12 weeks (n=4).
GL-ONC1 administered iv is well tolerated with preliminary evidence of anti-tumour activity.