Hyperthermia Combined With Immune Checkpoint Inhibitors in the Treatment of Advanced Gastrointestinal Malignancies With Liver Metastases

Hyperthermia Combined With Immune Checkpoint Inhibitors in the Treatment of Advanced Gastrointestinal Malignancies With Liver Metastases: A Multicenter, Open-label, Dual-cohort Phase II Exploratory Clinical Study

This study aims to explore the synergistic antitumor effects and safety of hyperthermia combined with immune checkpoint inhibitors (ICIs) in patients with advanced gastrointestinal malignancies with liver metastases. Liver metastasis represents a common cause of treatment failure in gastrointestinal cancers, and the response rate to ICIs remains suboptimal in certain patients with liver metastases, potentially attributable to the immunosuppressive hepatic microenvironment. The combination of hyperthermia with ICIs, chemotherapy, or other therapeutic modalities may further enhance treatment efficacy. Hyperthermia could potentially reverse immunosuppression and improve ICI effectiveness through mechanisms including enhanced tumor blood perfusion, promoted antigen presentation, and increased immune cell infiltration. This multicenter, open-label, dual-cohort phase II trial will evaluate patients stratified by tumor type (colorectal cancer versus gastric cancer) to assess the objective response rate (ORR), progression-free survival (PFS), and safety profile of hyperthermia-ICI combination therapy. Concurrently, dynamic monitoring of peripheral immune markers (such as neutrophil-to-lymphocyte ratio and interleukins) and tumor microenvironment alterations will be conducted to identify potential predictive biomarkers, thereby providing preliminary evidence for subsequent phase III investigations. The ultimate objective is to develop more effective combination treatment strategies for patients with advanced gastrointestinal malignancies accompanied by liver metastases.

Inclusion Criteria:

• Age between 18 and 75 years, male or female.
• Histologically or cytologically confirmed diagnosis of gastrointestinal malignancy with liver metastases.
• Prior treatment requirements:

Gastric cancer patients must have received at least one prior line of systemic therapy.

Colorectal cancer patients must have received at least two prior lines of systemic therapy.

• Clinically assessed as suitable for hyperthermia combined with immune checkpoint inhibitor therapy.
• At least one measurable lesion meeting RECIST 1.1 criteria.
• Expected survival ≥6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ and bone marrow function.
• Willingness to provide sufficient baseline and post-treatment samples, ability to comply with long-term follow-up and evaluation, and signed informed consent.
• No prior history of other malignancies.

Exclusion Criteria:

• Pregnant or lactating women.
• Any comorbidities or underlying medical conditions that, in the investigator's judgment, render the patient unsuitable for study participation.
• Presence of other severe physical or psychiatric disorders, or clinically significant laboratory abnormalities that may increase the risk associated with study participation, interfere with study results interpretation, or otherwise make the patient inappropriate for inclusion as determined by the investigator.