Oncolytic virus OH2 extends survival in patients with PD-1 pretreated melanoma: phase Ia/Ib trial results and biomarker insights
Xuan Wang, Hui Tian, Zhihong Chi, Lu Si, Xinan Sheng, Han Hu, Xiangyong Gu, Siming Li, Caili Li, Bin Lian, Li Zhou, Lili Mao, Bixia Tang, Xieqiao Yan, Xiaoting Wei, Juan Li, Binlei Liu, Jun Guo, Yan Kong, Chuanliang Cui
Abstract
BACKGROUND: OH2 is an oncolytic virus derived from herpes simplex virus type 2. A phase Ia/Ib clinical trial in China was conducted in patients with unresected stage III-IV melanoma, the majority of whom had the acral type, to assess the safety and preliminary efficacy of OH2. METHODS: represents cell culture infectious dose 50%) while six patients underwent multidose therapy. Phase Ib expanded the proposed dose. Antitumor efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors and immune-RECIST guidelines. NCT04386967 is the clinical trial identifier. RESULTS: All 44 patients were enrolled. OH2 was well tolerated without serious adverse events (AEs) or deaths reported. No Grade 3 or higher treatment-related AEs occurred. In phase Ia, the 1-year survival rate was 92.9% (95% CI, 59.1% to 99.0%), with a median overall survival of 28.9 months (95% CI, 12.7 to not reached). In phase Ib, 10 patients achieved immune-partial response (iPR)/partial response (PR), yielding an objective response rate (ORR) of 37.0% (95% CI, 19.4% to 57.6%), with 6 patients still responding. The rate of the durable response (PR or complete response lasting at least 6 months) was at least 29.6% (8/27). Notably, 7 of 12 III-IVM1a patients who previously received programmed cell death protein-1 (PD-1) therapy achieved iPR/PR, with an ORR of 58.3% (95% CI, 27.7% to 84.8%) and a disease control rate of 75.0% (95% CI, 42.8% to 94.5%). Biomarker analysis indicated that elevated baseline neutrophil activation state correlated with poorer clinical outcomes. A phase III clinical trial is ongoing in China (NCT05868707). CONCLUSIONS: OH2 oncolytic virotherapy exhibited a favorable safety profile without dose-limiting toxicities (DLTs) and demonstrated durable antitumor efficacy in patients with melanoma, especially in those who had progressed on anti-PD-1 treatment. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04386967.