OrienX010 oncolytic viral therapy in phase Ic trial of intralesional injection in liver metastases among patients with stage IV melanoma after standard treatment.

Abstract

e21013 Background: The liver is one of the most common metastases in melanoma pts and associated with extremely poor prognosis. However, effective treatment has not been found. The safety and efficacy of OrienX010, a herpes simplex virus type 1-derived oncolytic immunotherapy with expression of gene encoding human GM-CSF, was tested in phaseⅠc trial of intralesional injection in liver metastases among patients with stage IV melanoma after standard treatment. Methods: We studied safety and efficacy of OrienX010 (8×107pfu/ml, 10ml per injection) q2w by ultrasound guided puncture. Efficacy was evaluated q8w by CT scan. The primary endpoint was toxicity. Secondary endpoints included Objective Response Rate (ORR), Disease Control Rate (DCR) as well as PFS time. Treatment continued until intolerance, or disease progression per Immune Related Response Criteria. Results: From May 2016, 15 pts received OrienX010 intralesional therapy. The median age was 47 y (32, 61), and 53.3% were female. The primary anatomic sites were: 40.0% (6 pts) from ocular, 33.3% (5 pts) from acral, 26.7% (4 pts) from mucosal. Only 1 patient with c-Kit mutation, 14 pts were wide-type in genotype. All pts had received at least one prior therapy, 53.3% (8 pts) had received transcatheter hepatic arterial chemoembolization. 73.3% (11 pts) had multiple liver metastases, 60.0% (9 pts) had extrahepatic metastases such as lung, bone, abdominal, distant lymph node. 60.0% (9 pts) had an elevation of serum LDH. Mean injection times were 6 (4-18). Mean size of all injectable lesions was 30.4mm (10.0-59.0). AEs were all grade 1/2, pyrexia 80.0%, fatigue 33.3%, injection site pain 26.7%, nausea/vomiting 20.0%, hepatotoxicity 20.0%, leucopenia 6.7%. 12 pts were eligible for evaluation till Jan 2017, and the median follow-up time was 6.0 months. ORR was 8.3% (1 PR), DCR was 41.7% (1 PR, 4 SD). Time to response was 8-16 wks, median PFS was 13.3 wks (95%CI 8.3-18.4), OS was not reached. Conclusions: This is the first trial for evaluating OrienX010 of intralesional injection in liver metastases among melanomas. It appears to be tolerable and with a potentially beneficial effect. Phase 2 and combination trial are pending.