Oncolytic virus OH2 extends survival in patients with PD-1 pretreated melanoma: phase Ia/Ib trial results and biomarker insights.

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: The trial enrolled patients with histologically confirmed unresectable stage III or advanced stage IV melanoma. In phase Ia, nine patients received OH2 single-dose treatment across three dose levels (10⁶, 10⁷, and 10⁸ CCID₅₀/mL, where CCID₅₀ 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.