Phase I, dose-escalation study hepatic artery infusion
No dose-limiting toxicity. Commonly mild to moderate fever, rigors and fatigue.
Objective response with chemotherapy + virus in a patient who was refractory to both 5-FU and ONYX-015 as single agents. 2 high dose patients had stable disease on combination therapy lasting from 7 to 17 months.
Metastatic liver deposits from gastrointestinal primaries
27
Phase II, hepatic artery infusion in combination with 5 FU and leucovorin
2 patients had reversible grade 3/4 hyperbilirubinemia and 1 patient had a reversible severe systemic inflammatory response.
3 patients with partial responses, 4 with minimal responses, 9 with stable disease, and 11 with progressive disease. Unclear from this study whether observed responses were due to viral treatment or chemotherapy or combination.
Metastatic colorectal cancer refractory to conventional therapy
24
Phase I/II, hepatic artery infusion
No dose-limiting toxicity was observed.
Overall median survival was 10.7 months. 2 patients had partial responses (tumur vol reductions of 66% and 72%). 11 patients had stable disease after viral treatment and median survival in this group was 19 months.
E1A under control of the rat probasin promoter E1B under control of the PSA promoter-enhancer
Hormone-refractory metastatic prostate cancer
23
Phase I, single intravenous infusion
Mostly grade 1 or 2 flulike symptoms were observed. There were 8 grade 3 events (fever or fatigue). At higher doses, asymptomatic grade 1 or 2 transaminitis were reported.
No partial or complete tumour responses were observed. 5 patients had a decrease in serum PSA of 25% to 49% following a single treatment.
ICP0 & ICP4-ve Only 1 copy of γ134.5 Transgene inserted HSV-1 TK gene (α4)
Hepatic colorectal metastases refractory to first-line chemotherapy
12
Phase I, dose-escalation study, hepatic artery infusion
Mild or moderate in severity, and self-limiting
Tumour response assessed at 28 days after viral delivery. 7 patients had stable disease. 2 patients had a partial response (tumour vol reductions of 39% and 20%). Median survival for this group was 25 months.
ICP0 & ICP4-ve Only 1 copy of γ134.5 Transgene inserted HSV-1 TK gene (α4)
Advanced metastatic colorectal
Phase 1 = 13, Phase 2 = 19
Phase I/II study, hepatic artery infusion treatment followed by two or more cycles of conventional chemotherapy
Mild-to-moderate febrile reactions after each NV1020 infusion. Grade 3/4 transient lymphopenia in two patients
After completion of NV1020 administration, 50% showed stable disease. Best overall tumor control rate after completion of combined therapy was 68% (1 partial response, 14 stable disease). Median time to progression was 6.4 months. Median overall survival was 11.8 months. One-year survival was 47.2%.
TK-ve Transgene inserted in TK region hGM-CSF (pE/L) and Lac-Z (p7.5)
Metastatic solid tumour disease which is refractory to conventional therapy specifically: Melanoma, Lung Cancer, Renal cell cancer, SCC of head and neck
23
Phase I, Dose Escalation Study
No dose-limiting toxicities. Mild flu-like symptoms were common.
Demonstrated that at the higher doses used ( to PFU/kg) JX-594 can selectively infect, replicate and express transgene products in target tumour tissue whilst sparing normal tissue. Although not designed for efficacy, one patient had partial response.