Phase Ic trial of intralesional OrienX010 oncolytic viral therapy into liver metastases among melanoma patients

Abstract

Background: Liver is a common metastatic site with poor prognosis for melanoma patients, yet limited efficacy has been shown in systemic therapy. OrienX010, a herpes simplex virus type 1-derived oncolytic immunotherapy with expression of gene encoding human GM-CSF, which has shown its efficacy in intralymphatic diseases, was tested for its safety and efficacy in phase Ic trial of intralesional injection into liver metastases. Methods: OrienX010 (8 x 107pfu/ml, 10ml per injection) was given intralesionally by ultrasound guide q2w, dose was distributed into 1-2 liver lesions according to tumor size. Tumor assessment was done q8w by CT scan. The primary endpoint was toxicity, secondary endpoints included ORR, DCR and PFS time. Treatment continued until intolerance, or disease progression per iRECIST. Results: From May 2016, 19 pts have been enrolled, 57.9% male with median age 47 years (32, 61). Mean size of injectable lesions was 30.4mm (10.0-59.0). One had c-Kit mutation (exon 9), no BRAF mutation. All pts had received at least one prior therapy, most (68.4%) were transcatheter hepatic arterial chemoembolization. 79.0% had mul-tiple liver metastases, 57.9% had extrahepatic metastases including lung, bone, abdominal, and distantlymph node. 57.9% had an elevation of serum LDH. Mean injection times were 6 (4-18). AEs were all grade 1/2, pyrexia 84.2%, fatigue 31.6%, injection site pain 26.3%, nausea/vomiting 21.0%, hepatotoxicity21.0%, leucopenia 10.5%. 12 patients were evaluable till Jan 2017 with median follow-up time of 6.0 months. ORR was 8.3% (1 PR), DCR 41.7% (1 PR, 4SD) with a time to response 8-16 wks, median PFS was 13.3 wks (95%CI 8.3-18.4), OS not reached. Conclusions: This is the first trial for evaluating intralesional oncolytic virus injection into liver metastases among melanoma pts-It is tolerable with a potentially beneficial effect. Phase 2 and combination trials are pending.