e14666 Background: The immunotherapy of bone and soft tissue sarcomas remains a challenge. Our pre-clinical trial confirmed that the combination of Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and OX-40 agonist had prominent synergistic effects. Immunoradiotherapy, especially Stereotactic Body Radiotherapy (SBRT) could further activate specific immune response. We hypothesized that intratumoral injection of “RO” (R837+αOX40) combined with SBRT will realize tumor control and reduce adverse reactions. Meanwhile, the synergetic application of PD-1 mAb systematically will improve the effectiveness of immunotherapy. Methods: This is a single-arm, single-center, open-label, exploratory trial that explore intratumoral injection of an emulsion of “RO” in combination with SBRT as “in situ vaccination” for advanced solid tumor (Ethics number: 2021-133-02). The inclusion criteria included: 1) advanced solid tumors which progress after standard therapies, 2) presence of one or more injectable lesions. SBRT to injected lesions was at a dose of 5-8Gy per fraction at a total dose of 20-32Gy. Imiquimod (0.75mg/ml) and αOX40 (2.5mg/ml) were prepared as emulsion and intratumoral injected into the target lesion for 4 times. Patients were also systematically administrated with PD-1 mAb (serplulimab). The primary endpoint was objective response rate (ORR) of target lesions. The secondary endpoint mainly included disease control rate (DCR) of target lesions, progression free survival (PFS), overall survival (OS), and clinical benefit rate (CBR), etc. Results: From May 2021 to October 2022, 30 patients were eligible for this trial (60% were sarcomas). 46.7% and 33.3% had received radiotherapy or PD-1/PD-L1 mAb respectively before. The ORR, DCR and CBR of target lesions were 29.2%, 91.7% and 41.7%, while these of systemic efficacy were 21.7%, 82.6% and 17.4%, respectively. In sarcomas, the ORR, DCR and CBR of target lesions were 25.0%, 93.8% and 50.0%, while these of systemic efficacy were 20.0%, 93.3% and 26.7%, respectively. Systemic median PFS were 3.67 months. The median event-free survival (EFS) of target lesions and median OS were not reached. Among the evaluable target lesions, 6-month EFS was 85.7% in sarcomas (6/7) and 76.9% in all patients (10/13). The most common TRAEs were leukopenia (50%), hypoproteinemia (30%) and anemia (20%), demonstrating that treatment is tolerable. Grade≥3 treatment-related adverse events (TRAE) occurred in 3 patients, including myocarditis (6.7%) and thyroiditis (3.3%). Conclusions: In situ vaccination with “RO” emulsion, along with SBRT was tolerable and induced anti-tumor immunity, which would also trigger systemic response when synergized with PD-1 mAb. This in situ vaccination has been proved to be a promising option for advanced solid tumors especially for sarcomas. Clinical trial information: ChiCTR2100053870 .