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Clinical Trial
. 2025 Feb 6;13(2):e010662.
doi: 10.1136/jitc-2024-010662.

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

Xuan Wang #  1 , Hui Tian #  1 , Zhihong Chi  1 , Lu Si  1 , Xinan Sheng  2 , Han Hu  3 , Xiangyong Gu  4 , Siming Li  1 , Caili Li  1 , Bin Lian  1 , Li Zhou  2 , Lili Mao  1 , Bixia Tang  2 , Xieqiao Yan  2 , Xiaoting Wei  1 , Juan Li  2 , Binlei Liu  4 , Jun Guo  2 , Yan Kong  5 , Chuanliang Cui  6
Affiliations
Clinical Trial

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

Xuan Wang et al. J Immunother Cancer. .

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.

Keywords: Immunotherapy; Neutrophil; Oncolytic virus; Skin Cancer.

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Conflict of interest statement

Competing interests: JG serves consulting/advisory roles in Merck Sharp & Dohme, Roche, Bayer, Novartis, Simcere Pharmaceutical Group and Shanghai Junshi Biosciences. LS has received speakers’ honoraria from MSD, Roche, Novartis, and Shanghai Junshi Biosciences. BL is the founder of Wuhan Binhui Biopharmaceutical. XG is a salaried employee of Wuhan Binhui Biopharmaceutical. For the remaining authors, there are no conflicts of interest.

Figures

Figure 1
Figure 1. Response to OH2 treatment. Chronological change of target lesions from baseline in phase Ia (A) and in phase Ib (B). Maximal changes in tumor burden from baseline in injected lesions (C) and uninjected lesions (D) from phase Ib. Each bar represents an individual lesion, with colors corresponding to patients in different response categories. (E) A biopsy of the scalp nodule (injection lesion) of patient 027 was performed with a histological finding of malignant melanoma. The patient achieved a PR duration of 13.1 months after OH2 treatment. (F) Patient 026 was diagnosed in June 2019 with melanoma in the left foot heel with excision surgery and lymph node dissection. Observation lesion (non-injection lesion): after 12 months treatment, iliac artery lymph nodes (short diameter) decreased from 21 to 9 mm. iPR, immune-partial response; PR, partial response; PD, progressive disease; SD, stable disease; TL, target lesion.
Figure 2
Figure 2. (A) Kaplan-Meier survival curves. (B) Response of patients in subgroups of different disease stages and PD1 treatment states to OH2. Note: there was one case of unknown primary lesion and unknown tumor stage in subjects with PD-1- naïve status. DCR, disease control rate; iPR, immune-partial response; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein-1; PR, partial response; PD, progressive disease; SD, stable disease.
Figure 3
Figure 3. (A) Representative box plot of the differentially expressed proteins between the clinical benefit and clinical non-benefit group before treatment (baseline) were measured with Olink and expressed as NPX units (left panel). GO enrichment analysis based on the nine differentially expressed proteins (middle panel). KEGG enrichment analysis based on the nine differentially expressed proteins (right panel). (B) Representative box plot of the differentially expressed proteins between the clinical benefit and clinical non-benefit group after treatment (maximal efficacy time) were measured with Olink and expressed as NPX units (left panel). GO enrichment analysis based on the 21 differentially expressed proteins (middle panel). KEGG enrichment analysis based on the 21 differentially expressed proteins (right panel). A t-test was performed to analyze the difference between the differentially expressed proteins. (C) immune cell counts of patients in the clinical benefit cohort and clinical non-benefit cohort at baseline. GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes.
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