Enhanced local and systemic efficacy in refractory solid tumors via integrated intra-tumoral injection and radiotherapy: A study of the ‘R-ISV-RO’ modality.

11558 Background: As for most refractory solid tumors, especially sarcoma, immunotherapy still lacks meaningful improvement in their outcomes. The novel 'R-ISV-RO' in situ vaccine, in which we merged radiotherapy, intratumoral delivery of R837 and OX-40 ligand, together with systemic use of immune-checkpoint blockades, may be clinically beneficial. Methods: This was an exploratory, single-center, single-arm clinical trial aimed at evaluating the efficacy and safety of the 'R-ISV-RO' in situ vaccine therapy for advanced solid tumors. Thirty patients aged 18 years or older with advanced solid tumors and at least one measurable lesion were enrolled. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), time to progression (TTP), and clinical benefit rate (CBR). The safety of the treatment and the injection procedures were also evaluated. Results: The ORR and DCR for injected lesions were 44.4% and 96.3%. Sarcoma patients exhibited superior outcomes, with a 100% DCR in injected lesions. The median PFS was 15.9 months for injected lesions and median OS was 23.6 months. The abscopal effect occurred in 12 patients. 'R-ISV-RO' treatment was well tolerated, with only 6.7% of patients experiencing grade 3 or higher adverse events. Improved clinical responses were associated with enhanced CD4⁺/CD8⁺ T-cell infiltration and peripheral expansion. Metabolomics analysis revealed therapy-induced metabolic remodeling. Conclusions: In this exploratory trial, 'R-ISV-RO' with concurrent immunotherapy demonstrated promising efficacy for both primary and distant tumors, especially for sarcomas. Systemic immune response and metabolic remodeling were also observed after the therapy. Clinical trial information: ChiCTR2100053870.