Safety and Efficacy of Canagliflozin in Patients With Locally Advanced or Advanced Solid Cancer

Summary

\*\*Revised version:\*\* Locally advanced or advanced solid tumors remain a major clinical challenge despite multimodal treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. For patients with unresectable, recurrent, metastatic, or treatment-refractory disease, prognosis remains poor, and effective therapeutic strategies are still urgently needed. Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 blockade, have transformed the treatment landscape of multiple solid tumors by reinvigorating anti-tumor immune responses through inhibition of the PD-1/PD-L1 pathway. However, only a subset of patients derive durable benefit from immunotherapy, and primary or acquired resistance remains common, highlighting the need for rational combination strategies to enhance anti-tumor efficacy. Intriguingly, sodium-glucose cotransporter 2 inhibitors, originally developed as anti-diabetic agents, have shown emerging anti-tumor potential through metabolic regulation and modulation of the tumor microenvironment. In particular, combining SGLT-2 inhibition with immune checkpoint blockade may enhance tumor control through metabolic-immunologic crosstalk. Preclinical evidence suggests that the SGLT-2 inhibitor canagliflozin may suppress tumor growth and potentially improve the efficacy of PD-1 blockade. Based on this rationale, this phase I trial investigates the safety and efficacy of canagliflozin combined with tislelizumab in patients with locally advanced or advanced solid tumors, evaluating its impact on progression-free survival, overall survival, objective response rate, and tumor microenvironment modulation. This study aims to explore a novel metabolic-immunotherapy strategy based on dual metabolic and immune regulation, potentially providing a new therapeutic option for patients with locally advanced or advanced solid tumors.

Timeline

Start

2026-09-10

Primary completion

2028-07-31

Completion

2028-07-31

Drugs

Indications