Safety and preliminary efficacy of OH2 combined with BS006 sequential intratumoral injection in patients with advanced solid tumors: An open-label, dose-escalation phase Ib/II study.

Abstract

2590 Background: The immunosuppressive (“cold”) tumor microenvironment (TME) limits patient response to checkpoint inhibitors. Oncolytic viruses (OVs) can selectively replicate in tumor cells, leading to robust TME-remodeling. Reported here is the first clinical evaluation of a dual TME-modulating strategy based on an oncolytic HSV2 platform, whereby OH2, a clinically validated oncolytic HSV2 expressing GM-CSF, which enhances tumor lysis, antigen release, and dendritic cell recruitment in the TME, is co-injected with BS006, a second HSV2-based OV, which expresses a PD-L1/CD3 bispecific antibody that can redirect bystander T cells to tumor cells in the TME. Methods: BS008-001 is a multicenter, open-label phase Ib /II trial in heavily pre-treated patients with advanced solid tumors. Patients received biweekly sequential intratumoral injections of OH2 (fixed dose: 10⁷ CCID₅₀/mL) followed by BS006 (dose escalation: 10⁶–10⁷ CCID₅₀/mL), with identical volumes being injected at the same lesion. The primary endpoint is safety and tolerability; secondary endpoints included efficacy outcomes assessed by RECIST 1.1/iRECIST. Results: As of January 5, 2026, a total of 15 patients with a mean age of 59.3 were enrolled (4 soft tissue sarcoma, 3 colorectal cancer, 2 melanoma, 2 biliary tract tumors, 2 breast cancer, 1 pancreatic cancer, and 1 liver cancer). 93.3% of the patients had a baseline ECOG score of 1. The mean maximum diameter of the target lesion at baseline was 91.3 mm. 100% of the patients had distant metastases to internal organs such as the liver and lungs. Safety: Incidence of TRAEs in the Safety Set was 53.3% (8/15) with mild grade 1-2 reactions, including fever (40.0%) and decreased lymphocyte count (20.0%). 1 patient developed Grade ≥3 TRAE (6.7%), but no DLT-causing AEs or premature withdrawal from the trial occurred. Efficacy: In the 13 patients with evaluable advanced multi-line solid tumors, ORR was 7.7% and DCR 38.5%. 1 melanoma patient achieved 1 PR after 11 treatments, with the total diameter of the target lesions significantly decreasing by 70.8% to 30.4 mm; another melanoma patient received 39 doses over a treatment duration of 18.9 months (SD), whereas 1 subject with leiomyosarcoma achieved SD and survived for 27.1 months. While the mOS of the 15 patients has not yet been reached, landmark 1-year OS is 78% (95% CI: 47%-92%), with 3 patients still on treatment. Conclusions: Sequential intratumoral administration of OH2 and BS006 in heavily pre-treated patients is feasible and safe and results in reasonable DCR, with some patients achieving long-term clinical benefits. This study supports the clinical relevance of an HSV2-based platform combination of 2 oncolytic viruses encoding GM-CSF and T-cell redirected bispecific antibodies to warm up the cold TME. Further clinical research of the platform is warranted.