An open-label single-center investigator-initiated exploratory clinical study in patients with refractory or recurrent solid tumors: R-ISV-FOLactis trial.

2640 Background: Soft tissue sarcomas (STSs) are a highly complex group of tumors and the treatment still remains a challenge. Immunotherapy has become a powerful clinical strategy, especially the application of therapeutic tumor vaccine. Hypofractionated radiotherapy (HFRT) can serve as an in situ vaccine and provide durable local control. We also develop a bifunctional engineered Lactococcus lactis (FOLactis) which expresses an encoded fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand to conduct in situ vaccination (ISV). In this study, we establish a novel R-ISV-FOLactis strategy, which refers to the combination of HFRT, intratumoral (IT) injection of FOLactis and synergetic anti-PD-1 therapy, to further enhance efficacy and realize the activation of the whole immunity cycle. Methods: This study is an open-label, single-center trial aimed at patients with advanced STSs who are unresponsive or intolerable to previous standard treatment. Patients will be treated with HFRT, the IT injection of FOLactis and PD-1 inhibitors. The primary endpoint is the objective response rate (ORR) of target lesions at 3 month and 6 month. The secondary endpoint includes the disease control rate (DCR) of target lesions, progression-free survival (PFS), overall survival (OS), etc. Results: This study started from July 2022 and ended in December 2023, involving 30 eligible patients with solid tumors and 16 of them are patients with STSs. The ORR and DCR of all target lesions after three months are 27.6% and 93.1% respectively, and in sarcomas, the ORR and DCR are 11.1% and 88.9%. We calculate the ORR and DCR of target lesions after six months, which are 56.3% and 100% respectively, and in sarcomas, these are 41.7% and 100%. Systemic median PFS are 2.87 months. Median PFS of target lesions has not been reached. Among the evaluable target lesions, 6-month EFS is 50% in sarcomas (6/12) and 50% in all patients (8/16). We test the level of cytokines before and after the first treatment and find that the changes in the percentage of CD8+ T cells, CD103+CD8+ T cells and CD39+CD8+ T cells have significance. Moreover, in sarcomas, PFS is relevant to the level of CD103+CD8+ T cells before treatment, CD39+CD8+ T cells after treatment, NK cells before treatment and immature DC cells after treatment. The most common treatment-related adverse events (TRAEs) are fever (83.3%), lymphocytopenia (53.3%), hypocalcemia (30%), neutrophilia (26.7%) and nausea (26.7%). Grade≥3 TRAEs occur in 11 patients, including lymphocytopenia (30%), fever (6.7%), leukopenia (3.3%), anemia (3.3%) and cardiac insufficiency (3.3%). Conclusions: The R-ISV-FOLactis strategy demonstrates its efficacy among patients with advanced STSs and induces certain anti-tumor immunity. The ISV of “FOLactis” may provide a promising option in the treatment of recurrent or refractory solid tumors. Clinical trial information: ChiCTR2200060660 .