The safety and efficacy of in situ vaccine FOLactis for advanced hepatic malignancies.

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: ORR difference of 33.3% favouring immunoradiotherapy combination

• Primary Outcome: Objective response rate (ORR) by RECIST v1.1: Group A 33.3% vs Group B 0% for targeted lesions

• Nnt Or Sensitivity: Number needed to treat approximately 3 based on ORR difference, but highly uncertain due to small sample size

• Confidence Interval: Group A ORR: 12.1-64.6% (extremely wide due to small sample)

Clinical Application

Currently not feasible - FOLactis vaccine experimental and not commercially available Not applicable to Australian practice. Vaccine not TGA-approved. Would require extensive Phase II/III trials before consideration for PBS listing. RACGP guidelines do not address experimental cancer vaccines Highly selected patients with advanced hepatic malignancies in research settings only

Abstract

BACKGROUND: Recent years have witnessed the emergence of a novel research direction in the field of tumor vaccines. An in situ vaccine known as FOLactis, comprised of genetically engineered Lactococcus lactis expressing a fusion protein of Fms-like tyrosine kinase 3 ligand (Flt3L) and co-stimulator OX40 ligand (OX40L), was developed by the Oncology Centre of Nanjing Drum Tower Hospital. The present study was designed to evaluate the efficacy and safety of combination therapy based on intratumoral injection of the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody in combination with immunoradiotherapy or low-dose chemotherapy in the treatment of advanced hepatic malignancies. METHODS: In this exploratory clinical study, patients with advanced hepatic malignancies were enrolled and randomly assigned to Group A and Group B, corresponding to different treatment regimens. The treatment regimen in Group A consisted of the in situ vaccine FOLactis combined with a PD-1 monoclonal antibody and immunoradiotherapy (5Gy/fraction×3fractions). In contrast, the regimen in Group B included the in situ vaccine FOLactis, a PD-1 monoclonal antibody, and low-dose chemotherapy (cisplatin plus vincristine). All treatments were given in 21-day cycles. The primary observation indicator of the study was the objective response rate (ORR) as defined by RECIST v1.1. Secondary observation indicators included the disease control rate (DCR) and the incidence of adverse events. RESULTS: A total of 18 eligible patients were included in the study. In Group A, the ORR and DCR for targeted lesions were 33.3%(95%CI:12.1-64.6%) and 77.8%(95%CI:45.3-96.1%), while the ORR and DCR for non-targeted lesions were 22.2%(95%CI:3.9-54.7%) and 66.7%(95%CI:35.4-87.9%), respectively. Targeted and non-targeted lesions in Group B did not reduce significantly, and their respective DCRs were 66.7%(95%CI:35.4-87.9%) and 22.2%(95%CI:3.9-54.7%). Patients in Group A experienced no significant adverse events. Patients in Group B experienced grade 1-2 hyperthermia as a side effect. CONCLUSIONS: The combination therapy based on the in situ vaccine FOLactis and intravenous PD-1 monoclonal antibody showed a certain degree of anti-tumor effect, and was safe and well tolerated in patients with advanced hepatic malignancies. TRIAL REGISTRATION: The Ethics Committee of Nanjing Drum Tower Hospital approved this study (approval number 2022-101-01). The associated trial is registered at ChiCTR.gov.cn (ChiCTR2200060660).

References

1. 1.Zhou, Z., Lu, X., Hu, L., Zhu, S., Qi, L., Zhu, X., & Shen, J. (2026). The safety and efficacy of in situ vaccine FOLactis for advanced hepatic malignancies. Vaccine, Article 128377. https://doi.org/10.1016/j.vaccine.2026.128377