Toll-like receptor 7 (TLR7) agonists and OX40 agonists injection combined with SBRT in advanced tumor patients.

e14645 Background: Currently, the mainstream approach for in situ vaccines involves radiotherapy or intratumoral injection of immunologic adjuvants. Hypofractionated stereotactic body radiotherapy (SBRT) has been demonstrated to be more effective in inhibiting tumor progression. We have developed a compound immune adjuvant (RO adjuvant) composed of Toll-Like receptor 7 (TLR7) agonists (imiquimod/R837) and OX40 agonists, combining with SBRT as “R-ISV-RO”. This approach integrated with anti-PD-1 immunotherapy, is designed to achieve a synergistic effect and thereby optimise patient survival. Methods: This was a single-center, single-arm, open-label phase 2 clinical trial, aimed at assessing the safety and efficacy of “R-ISV-RO” combined with anti-PD-1 monotherapy in patients with advanced solid tumors. Enrolled patients was received SBRT with four image-guided intratumoral injections of RO adjuvant on days 3, 6, 22, and 28. The primary endpoints of this study are safety and tolerability. Adverse events were systematically assessed according to the Common Terminology Criteria for Adverse Events, version 5.0. Anti-tumour efficacy was defined as access based on Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Secondary endpoints include target lesion (injected) disease control rate, clinical benefit rate, progression-free survival, overall survival. Results: 30 patients aged 21 to 72 years were enrolled, including 18 cases of sarcoma and 12 cases of other tumour types. 28 patients experienced grade 2 or higher adverse events. Leukopenia was the most common adverse event, occurring in 15 cases, followed by 9 cases with hypoalbuminemia. Two patients experienced grade 3 or higher adverse events, including immune-related hypothyroidism and immune-related myocarditis. Until March 26, 2024, The median overall survival (OS) of the patients was 454 days. At the 3-month assessment, the overall therapeutic efficacy demonstrated an objective response rate (ORR) of 15.4% and a disease control rate (DCR) of 50%, while at the 6-month assessment, the ORR was 8% and the DCR was 16%. For the target lesions, the 3-month ORR was 32% and the DCR was 96% and 6-month ORR was 47.4%, achieving a DCR of 89.5%.Patients exhibited an overall PFS of 3.6 months, while the PFS of target lesions reached 6.1 months. This may indicate that the intervention is capable of effectively suppressing local lesions. In fact, subjects with higher levels of post-treatment T helper 9 cells (Th9 cells) have better survival rates in terms of both OS and progression-free survival (PFS). Furthermore, it can also be observed that the OS of the post-treatment T-regulatory cell group is significantly longer than the other group. Conclusions: “R-ISV-RO” combined with anti-PD-1 mAb has demonstrated reliable safety as well as encouraging efficacy in both overall and target lesion responses. The study is still ongoing. Clinical trial information: ChiCTR2100053870 .