A phase 1/2 clinical trial has revealed promising results for the combination of oncolytic virus OH2 with PD-1 inhibitor HX008 in treating patients with locally advanced or metastatic sarcoma, according to findings published in the Journal for ImmunoTherapy of Cancer.
The study demonstrated meaningful clinical activity, particularly when the two agents were combined. While OH2 monotherapy showed no responses in evaluable patients (n=7), the combination therapy achieved an overall response rate of 16.7% among 18 evaluable patients, including two complete responses.
Survival Outcomes and Safety Profile
At a median follow-up of 11.9 months, the combination therapy demonstrated substantial survival benefits. The median overall survival reached 18.04 months for patients receiving OH2 plus HX008, compared to 4.50 months with OH2 monotherapy. Progression-free survival was similar between groups at 1.45 months and 1.41 months, respectively.
The safety profile proved favorable, with no dose-limiting toxicities observed during dose escalation. The maximum-tolerated dose of OH2 was not reached, and notably, no serious treatment-related adverse effects or deaths were attributed to the treatment.
Treatment Details and Patient Population
OH2, a genetically engineered oncolytic virus derived from herpes simplex virus-2 strain HG52, was administered intratumorally at doses ranging from 106 to 108 CCID50/mL every two weeks. Patients in the combination arm also received HX008 intravenously at 200 mg every three weeks.
The trial enrolled patients with diverse sarcoma subtypes, including leiomyosarcoma, angiosarcoma, and fibrosarcoma. Eligible participants had experienced disease progression within six months before enrollment and had received at least one line of standard systemic therapy.
Promising Results in Specific Subtypes
Particularly encouraging responses were observed in patients with angiosarcoma and fibrosarcoma. Among responding patients, duration of response ranged from 3.9 to 6.5 months. Notably, one angiosarcoma patient who had previously progressed on paclitaxel plus an immune checkpoint inhibitor showed response to the combination therapy, suggesting potential synergistic effects.
Safety Analysis
The combination therapy demonstrated manageable toxicity, with 84.2% of patients experiencing treatment-related adverse events. Common side effects included fever (26.3%), elevated γ-GGT levels (26.3%), and weight loss (21.1%). Grade 3 or higher adverse events were limited and included hypertriglyceridemia, nausea, anorexia, and neck pain, each occurring in 5.3% of patients.
These findings open new avenues for investigation, particularly in neoadjuvant settings for specific sarcoma subtypes. The study authors emphasized that the combination's effectiveness and low toxicity profile warrant further exploration, especially in selective soft tissue sarcoma subtypes where treatment options remain limited.
