Efficacy of multimodal thermal therapy combined with immune checkpoint inhibitors and chemotherapy in unresectable pancreatic cancer with liver metastases.

e16392 Background: Although combined with immune checkpoint inhibitors (ICIs), the prognosis pancreatic cancer with liver metastases (PCLM) remains unsatisfactory, due to immunosuppressive tumor microenvironment. Multimodal thermal therapy (MTT) is a novel treatment method consisting of continuous rapid freezing, natural thawing, and radiofrequency heating, effectively remodel the immune environment, and trigger long-term systemic antitumor immunity. This study aims to explore the primary application of MTT combined with subsequent ICIs-based systemic therapy in PCLM. Methods: Patients aged 18–70 years with primary diagnosed, unresectable PCLM were enrolled in this single-center, prospective clinical trial. Participants received MTT on at least one of the liver metastases combined with subsequent ICIs and chemotherapy (camrelizumab 200 mg IV on Day 1, gemcitabine 1000 mg/m² IV, and nab-paclitaxel 125 mg/m² IV on Days 1 and 8, every 3 weeks for 6 cycles), which was started on day 7 post MTT. The primary endpoints were safety and efficacy. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Exploratory endpoints included immune marker changes induced by MTT. Results: Five patients were enrolled in this study, and well tolerated with MTT. The treated liver tumors were completely ablation. One patient withdrew due to autoimmune hepatitis after the first ICIs treatment. During the follow-up period (9.9-15.1 months), the other four patients were all alive. The pancreatic lesions of these four patients were assessed as partial response (PR). The non-ablated liver lesions were assessed as partial response (PR) in two patients, stable disease (SD) in one patient, whereas one patient developed new liver lesions. One patient achieved success conversion and underwent curative surgery 6 months after MTT. Peripheral blood immune cells single-cell-sequencing revealed that MTT promoted the phenotypic maturation of myeloid cells including enriched antigen presentation signaling and upregulated expression level of inflammatory cytokines. The effector functions of T cells were also enhanced post-treatment, also accompanied by the increased level of PD-1, which provided the basis for anti-PD-1 treatment after MTT. Conclusions: MTT as a novel and safe promising therapy can systematically activate innate and adaptive antitumor immunity, potentially enhances the efficacy of immunotherapy and chemotherapy medicines. This modality offers new possibilities for downstaging and conversion therapy in PCLM. Clinical trial information: NCT06307080 .