A phase I trial on the safety, tolerance, and preliminary efficacy of intracavitary injection of in situ vaccines (FOLactis) in patients with advanced solid tumors complicated with malignant pleural effusion.

Abstract

2601 Background: Malignant pleural effusion (MPE) is caused by the metastasis of malignant tumors to the pleura. Traditional treatment have limited efficacy. In our preliminary research, a recombinant lactobacillus expressing the fusion protein Flt3L-OX40L (enhancing antigen-presenting function of dentritic cells and activation of antigen-specific T cells) named FOLactis was proved to have strong anti-tumor effect in early clinical trials. This clinical study was designed to explore the safety and efficacy of intracavitary injection of FOLactis for the treatment of malignant pleural effusion (NCT06512896). Methods: This is a single arm, single center study. In addition to systemic treatment, participants received intracavitary 2-4 injections of FOLactis. Primary endpoint was safety; secondary endpoints included Objective response rate of pleural effusion and the duration time of pleural effusion control. Results: From June 2023 to Oct 2025, a total of 38 patients were intracavitary injected with FOLactis, of which 29 patients completed more than 2 injections. Among these patients, the adverse reactions included Grade I-II fever (12/38, 31.6 %), chest wall pain (9/38, 23.68%), fatigue (2/38, 5.26%), and pneumothorax (1/38, 2.63%), while no adverse events above grade III were observed. Among the 38 patients with local treatment efficacy evaluation, 10 patients had complete disappearance of pleural effusion (10/38, 26.32%), 24 patients had reduction of pleural effusion (24/38, 63.16%), 4 patients had no significant change in pleural effusion (4/38, 10.53 %). Up to the current date, there are 21 patients whose pleural effusion has been controlled for more than one year. Among them, one patient with with advanced lung adenocarcinoma have had their pleural effusion controlled for over 30 months and is still under follow-up. It was found that patients with reduced pleural effusion had higher baseline secretion levels of IL-5 (P=0.0217), TNF-a (P=0.0178) and IFN-a (P=0.0278) in pleural effusion, while those with significantly increased levels of IL-6 (P=0.0076), IL-1B (P=0.0009) and IL-8 (P=0.0198) after treatment also had better control of pleural effusion. Further analysis of RNA sequencing in the pleural fluid of 15 patients revealed that patients with better therapeutic effects showed upregulation of CD4 + memory T cells, lymphoid precursor cells, CD8 + effector memory T cells and an upward trend in immune microenvironment scores after treatment. Conclusions: This ongoing phase I study with intracavitary injection of FOLactis in patients with malignant pleural effusion has preliminarily confirmed safety and clinical efficacy, which suggested to be a promising immunotherapeutic strategy for the effective control of malignant pleural effusion. Clinical trial information: NCT:06512896 .