Background: Advanced melanoma with liver metastasis has a lower response rate and survival even in immunotherapy era which might because of its immunosuppressive tumor microenvironment. CPI combined with TVEC had showed a remarkable in cutaneous melanoma. The initial results of the phase 1b trial, systemic toripalimab (anti-programmed cell death-1 antibody) combined with Intratumoral injection of liver with OrienX010 - a HSV-1-derived oncolytic virotherapy with expression of GM-CSF in liver metastasis patients without extra-hepatic injectable lesions had shown its efficacy. Here we present the PFS and overall survival (OS) outcomes. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous toripalimab Q2W combined with ultrasound guided intratumoral injection of OrienX010 Q2W (8×10⁷ pfu/ml, 10ml per injection) until intolerance or disease progression per iRECIST criteria. Liver biopsy would be performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was toxicity; secondary endpoints included ORR, disease control rate (DCR), PFS and OS. NCT04206358. Results: From Jul 2019 to Feb 2023, 30 pts enrolled. 60.0% pts primary from mucosal,; 73.3% got extra-hepatic metastasis; median size of injected lesions: 24mm(10-94mm); median number of liver metastasis: 7(1-10); median number of injection: 10 (3-36). Among these pts, 29 pts could be evaluated for efficacy. The median PFS was 7.0months (95%CI: 4.7-9.3 months) and the median OS was not reached. The 3-year OS rates 51.5%. The global ORR by investigator was 20.7% (6/29), DCR 48.3% (14/29); the response rate was 31.0%(9/29) for injected lesions, 30.0%(6/20) for non-injected lesions in liver, and 27.8% (5/18) for extra-hepatic metastases. For pts（21.7%( 2 PR and 3 SD)）with no melanoma cells residual by immunohistochemistry in biopsies the median PFS was 14.0 months (95%CI: 3.7-24.4 months), and it was much longer than that of other pts which was 4.1 months (95%CI: 1.4-6.8 months). The median OS of the pts with no melanoma cells was 19.7 months (95%CI: 7.5-31.9 months). Most adverse events (AE) were grade 1-2 and manageable. The grade 3-4 treatment-related AE included elevated transaminase (3 [10.0%]), nausea (1 [3.3%]), pulmonary embolism (1 [3.3%]) and vomiting (1 [3.3%]). No treatment-related deaths occurred. Conclusions: Systemic toripalimab combined with intrahepatic OrienX010 injection has shown remarkable long PFS, OS and ORR in melanoma pts with liver metastases with manageable toxicity. Clinical trial information: Clinical trial information: NCT04206358.