Background

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.

Method

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.

Results

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).

Conclusion

  GL-ONC1 administered iv is well tolerated with preliminary evidence of anti-tumour activity.