Recombinant human adenovirus 5 injection plus toripalimab therapy in patients with advanced and refractory melanoma: A single arm, single-center, prospective study.

Abstract

e21503 Background: Treatment options are limited for patients with advanced melanoma and refractory melenoma, especially for acral and mucosal melanoma. Previous data showed that the objective response rate (ORR) of second-line PD1 monotherapy for acral and mucosal melanoma were 14-15.8% and 0-13.3%, respectively. We evaluate the safety and efficacy of recombinant human adenovirus 5 injection (oncolytic virus) plus toripalimab (PD-1 antibody) for patients who have progressed on checkpoint inhibitors, chemotherapy and anti-angiogenesis. Preliminary analysis of efficacy- related factors. Methods: Patients received the recombinant human adenovirus 5 injection (2ml) local lesions plus toripalimab 240mg systemic therapy every 2 weeks until progression or intolerable toxicity. The primary objective was safety and ORR. Secondary objective included progression-free survival (PFS) and disease control rate (DCR). Efficacy assessments were performed every 2 months according to RECIST v1.1 criteria. Blood samples were collected from patients prospectively. Serum interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, Tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured at baseline and after two cycles of treatment via flow cytometry. The peripheral blood neutrophils and lymphocytes were collected simultaneously. Results: Ten cases of patients were enrolled from November 2020 to January 2022. Baseline character:primary site (1 cutaneous melanoma; 5 acral melanoma; 4 mucosal melanoma), prior therapy (anti-PD1 100%; anti-angiogenesis 60%; chemotherapy 60%; second line and above 40%), 50% liver/bone lesions. All patients evaluated received at least 2 cycles of the combination regimen. The treatment-related adverse event was fever, accounting for 80%, and there were no other adverse events. The ORR was 20% (2PR) and the DCR was 70% (2PR, 5SD, 3PD). The 2-month PFS was 70%, and the median PFS has not yet been reached. Disease progression in 3 patients including liver and bone lesion. Higher baseline lymphocyte levels and lower neutrophil-to-lymphocyte ratio (NLR) values were found in the respongders compared with non-responders. The serum IL-6, IL-8, IL-10, and TNF-α levels were significantly increased in the responders after 2 cycles of treatment. Conclusions: The preliminary data showed that the combination of recombinant human adenovirus 5 injection plus toripalimab demonstrated acceptable toxicity and promising antitumor efficacy in patients with advanced and refractory melanoma, and promoted favorable changes in serum IL-6, IL-8, IL-10 and TNF-α levels in clinical responders. High baseline lymphocyte and low NLR values may be predictors of treatment response. Long-term survival data remain to continue with follow-up. It is worth to further validate the efficacy in a randomized prospective trial. Clinical trial information: 2000033959.