Phase II efficacy results using an oncolytic herpes simplex virus (NV1020) in patients with colorectal cancer metastatic to liver (mCRC)

4089 Background: NV1020 is a genetically engineered oncolytic Herpes virus. Published Phase 1 dose-ranging results reported no significant related toxicity except for a mild (<24 hr) viral syndrome. Initial Phase 2 tumor response data using the optimal biological dose (OBD) are now presented. Methods: Patients with heavily pretreated, progressing liver mCRC received 4 doses of NV1020 (1 X10 8 pfu) by weekly hepatic artery infusion followed by two cycles of conventional chemotherapy. Follow-up (≥1 year) evaluation included 4 X 3-monthly scans, then telephone contact to determine survival. Blinded, independent radiologists interpreted CT (modified RECIST) and FDG PET (EORTC) scans. Results: All 22 patients had prior 5FU-based treatment: 77% and 58% also had oxaliplatin or irinotecan, respectively (50% both agents); 86% had one targeted therapy (24% ≥2 such agents); 29% had radiofrequency ablation. Mean time from primary resection was 95 weeks, mean CEA was 182 ng/mL, and 55% had pulmonary lesions. Two patients received only 2 NV1020 infusions due to rapidly progressing disease. Virus tolerability was unchanged from Phase 1 and no related, serious or Grade 4 toxicity was found. NV1020 neutralizing antibodies rose in all patients but no NV1020 was shed (saliva, skin). After NV1020 alone, 10/22 (45%) and 8/20 (40%) on CT and PET, respectively, showed stable disease. 21 patients subsequently received chemotherapy, 45% with drugs to which they were previously refractory and 36% with only one new drug. 14% refused both planned cycles. Best response observed with CT was 55% (1 CR, 1 PR, 10 SD) and 59% (5 PR, 8 SD) with PET. Despite intrahepatic delivery, some remote responses were observed. Response did not correlate with initial tumor size, SUV, or CEA, with time since primary resection, pre- or post NV1020 chemotherapy type. Nine (41%) remain alive > 1 year. Kaplan-Meier median time to progression is 28 weeks (95% CI [9–37]); median survival probability is 52 weeks (95% CI [36–90]). Conclusions: NV1020 stabilizes liver metastases in highly advanced mCRC and may sensitize tumors to salvage chemotherapy resulting in extended overall survival. A controlled Phase 2/3 trial is justified. [Table: see text]