An open-label single-center investigator-initiated exploratory clinical study in patients with refractory or recurrent solid tumors using SBRT as “in situ vaccination”: R-ISV-FOLactis trial.
Authors: Rutian Li, Juanjuan Dai, Jie Shen, Xiaolu Wang, Jinfeng Bao, Xiaofeng Chang, Yingling Zhou, Wu Sun, Qin Wang, Shiyao Du, Siyi Tan, Junmeng Zhu, Xia Zhou, Qin Liu, Lijing Zhu, Baorui Liu
Journal: Journal of Clinical Oncology (2024)

44 Background: The immunotherapy of sarcomas remains a challenge. As a breakthrough tool for cancer immunotherapy, the therapeutic cancer vaccine is in rapid development. In situ vaccination can be realized by intratumoral immune injection and radiotherapy. We have developed a bifunctional engineered Lactococcus lactis (FOLactis) expressing an encoded fusion protein of fms-like tyrosine kinase 3 ligand (Flt3L) and OX40 ligand (OX40L). We hypothesized that intratumoral injection of "FOLactis" combined with SBRT will realize tumor control and the synergetic application of PD-1 mAb systematically will further improve the effect of immunotherapy. Methods: This exploratory clinical study is designed as an open-label trial aimed at treating patients with advanced solid tumors who are unresponsive or intolerable to standard treatment. Patients will be treated with SBRT, intratumoral injection of "FOLactis", and PD-1 blockade. The primary endpoint was the objective response rate (ORR) of target lesions after 3 months and 6 months. The secondary endpoint included the disease control rate (DCR) of target lesions, progression-free survival (PFS), overall survival (OS), etc. Results: From July 2022 to December 2023, 30 patients were eligible for this trial (63% were sarcomas). 53.3% and 33.3% had received radiotherapy or PD-1/PD-L1 mAb before respectively. The ORR and DCR of target lesions after 3 months were 27.6% and 93.1%, while these of systemic efficacy were 17.2% and 55.2%, respectively. In sarcomas, the ORR, DCR of target lesions were 11.1% and 88.9%, while these of systemic efficacy were 5.5% and 50%, respectively. Considering the deferred response in sarcomas, we also calculated the ORR after 6 months as the primary endpoint. The ORR, DCR of target lesions after 6 months were 56.3% and 100%, while these in sarcomas were 41.7% and 100%, respectively. Systemic median PFS were 2.87 months. Median PFS of target lesions and mOS has not reached. Among the evaluable target lesions, 6-month EFS was 50% in sarcomas (6/12) and 50% in all patients (8/16). Expression of CD4 + , CD8 + T cells and dendritic cells was significantly increased between pre-treatment and post-treatment peripheral blood in responders. The most common treatment-related adverse events (TRAEs) were fever (83.3%), lymphocytopenia (53.3%), hypocalcemia (30%), neutrophilia (26.7%) and nausea (26.7%). Grade≥3 TRAE occurred in 11 patients, including lymphocytopenia (30%), fever (6.7%), leukopenia (3.3%), anemia (3.3%) and cardiac insufficiency (3.3%). Conclusions: In situ vaccination with“FOLactis", along with SBRT was tolerable and induced anti-tumor immunity, which would also augment systemic response when synergized with PD-1 mAb. This in situ vaccination is probably a promising option for advanced solid tumors. Clinical trial information: ChiCTR2200060660 .