A phase 1/2 study published in the Journal for ImmunoTherapy of Cancer suggests that the oncolytic virus OH2, when combined with the PD-1 inhibitor HX008, is well tolerated and shows potential antitumor activity in patients with locally advanced or metastatic sarcoma.
In the study, patients receiving OH2 alone (n = 7) had an overall response rate (ORR) of 0%, while those receiving OH2 plus HX008 (n = 18) achieved an ORR of 16.7%, including two complete responses. After a median follow-up of 11.9 months, the median progression-free survival (PFS) was 1.41 months (95% CI, 1.15-2.73) for the monotherapy group and 1.45 months (95% CI, 1.38-5.36) for the combination group. Median overall survival (OS) was significantly higher in the combination group at 18.04 months (95% CI, 8.90-not available) compared to 4.50 months (95% CI, 1.91-8.21) in the monotherapy group.
Regarding safety, no dose-limiting toxicities were reported, and the maximum tolerated dose of OH2 was not reached during dose escalation. There were no serious treatment-related adverse events (TRAEs) or deaths attributed to the study treatment.
“Our findings support further research into oncolytic virus therapies combined with immune checkpoint inhibitors for sarcoma,” the study authors wrote. “This approach may be particularly relevant in neoadjuvant settings for certain sarcoma subtypes, such as angiosarcoma and fibrosarcoma.”
OH2 is a genetically engineered oncolytic virus derived from the herpes simplex virus (HSV)-2 strain HG52. It is designed with the human granulocyte-macrophage colony-stimulating factor (GM-CSF) encoding gene and lacks the ICP34.5 neurovirulence gene.
Study Design and Patient Characteristics
This open-label, non-randomized, multicenter trial enrolled patients with locally advanced or metastatic soft tissue sarcoma who had experienced disease progression within six months prior to enrollment. Eligible participants were at least 18 years old, had at least one injectable lesion with a maximum diameter of 5 mm, had received at least one prior line of systemic therapy, and had adequate organ function.
Patients were assigned to receive either OH2 alone or in combination with HX008. OH2 was administered intratumorally at doses of 10^6, 10^7, or 10^8 CCID50/mL every two weeks. In the combination arm, HX008 was given intravenously at a fixed dose of 200 mg every three weeks. OH2 injections were delivered directly into cutaneous or subcutaneous lesions, or with ultrasound guidance for deeper tumors. The maximum volume per injection was 8 mL, with no restrictions on the number of treated lesions per patient.
The primary endpoints included safety and tolerability in phase 1 and ORR per RECIST 1.1 criteria in phase 2. Secondary endpoints included duration of response (DOR), PFS, and OS.
At baseline, the median age in the monotherapy (n = 7) and combination (n = 19) groups was 45 years (range, 25-65) and 54 years (range, 24-69), respectively. Most patients in both cohorts had distant metastases (71.4% vs 52.6%) and negative HSV-2 serostatus (100% vs 84.2%). Histological subtypes included leiomyosarcoma, angiosarcoma, bone sarcoma, rhabdomyosarcoma, fibrosarcoma, alveolar soft part sarcoma, liposarcoma, synovial sarcoma, and undifferentiated/unclassified sarcoma.
Additional Safety and Efficacy Data
Among the patients who responded to OH2 plus HX008, the group included one patient each with fibrosarcoma and liposarcoma, and two patients with angiosarcoma. One patient with liposarcoma experienced tumor shrinkage in injected lesions but had to discontinue treatment due to progression in non-injected areas. The three remaining responders had durations of response of 3.9 months, 5.5 months, and 6.5 months, respectively. Notably, one angiosarcoma patient who had previously progressed on paclitaxel plus an immune checkpoint inhibitor responded to the combination therapy, suggesting a possible synergistic effect. This patient remained on treatment at the data cutoff.
In the monotherapy group, 85.7% of patients experienced at least one TRAE, with fever (57.1%), anemia (28.6%), and decreased white blood cell count (28.6%) being the most common. Two patients developed grade 3 or higher anemia. In the combination group, 84.2% of patients reported TRAEs, with fever (26.3%), elevated γ-GGT levels (26.3%), and weight loss (21.1%) being most frequent. Grade 3 or higher TRAEs included hypertriglyceridemia, nausea, anorexia, and neck pain (each at 5.3%).
“Intratumoral OH2 injection demonstrated a favorable safety profile in sarcoma patients,” the study authors concluded. “Encouraging antitumor responses were seen in angiosarcoma and fibrosarcoma cases treated with OH2 and HX008. Given its efficacy and low toxicity, further investigation of OH2/HX008 as a neoadjuvant treatment for select sarcoma subtypes is warranted.”
” Reference Tan Z, Wu Y, Fan Z, et al. Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial. J Immunother Cancer. 2025;13(1):e010543. doi:10.1136/jitc-2024-010543″
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Resource:
oncologynews.com
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