ESTRO meets Asia 2024 - Abstract Book

S259

Interdisciplinary – Sarcoma/skin cancer/malignant carcinoma

ESTRO meets Asia 2024

33

Proffered Paper

An investigator-initiated clinical study using SBRT as “in situ vaccination”:‘R-ISV-FOLactis’trial

Rutian Li, Lijing Zhu, Juanjuan Dai, Xiaolu Wang, Jinfeng Bao, Xiaofeng Chang, Yingling Zhou, Wu Sun, Qin Wang, Shiyao Du, Siyi Tan, Junmeng Zhu, Xia Zhou, Qin Liu, Jie Shen, Baorui Liu

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, The comprehensive Cancer centre, Nanjing, China

Purpose/Objective:

The immunotherapy of sarcomas remains a challenge. As a breakthrough tool for cancer immunotherapy, the therapeutic cancer vaccine, which includes neoantigen vaccine and in situ vaccine, is in rapid development [1]. In situ vaccination can be realized by intratumoral immune injection and radiotherapy, especially Stereotactic Body Radiotherapy (SBRT) [2-3]. 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) [4]. 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.

Material/Methods:

This exploratory clinical study is designed as an open-label, single-center 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 blockades. The primary endpoint was the objective response rate (ORR) of target lesions at 3 month and 6 month. 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 median OS 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%).

Conclusion: