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OncoMatch/Clinical Trials/NCT07076823

Safety and Efficacy of Canagliflozin in Patients With Metastatic High Microsatellite Instability (MSI-H) Colorectal Cancer

Is NCT07076823 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies Canagliflozin for colorectal cancer.

Phase 1RecruitingWest China HospitalNCT07076823Data as of May 2026

Treatment: CanagliflozinColorectal cancer (CRC), ranking third in incidence among men and second in women globally with third-highest mortality in the US, remains a major health challenge despite multimodal therapies, particularly for advanced-stage patients with poor prognosis where immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 blockers have emerged as transformative agents by reinvigorating anti-tumor immunity through PD-1/PD-L1 pathway inhibition. While MSI-H CRC's high mutational burden renders it susceptible to immunotherapy, clinical trials demonstrate durable responses with domestic ICIs such as tislelizumab showing 41.2% ORR, 14.4-month PFS, and 28.7-month OS in metastatic MSI-H CRC, yet unmet needs persist. Intriguingly, SGLT-2 inhibitor exhibit promising oncolytic potential, particularly when combined with ICIs, as evidenced by observational studies revealing enhanced tumor control in pancreatic ductal adenocarcinoma through metabolic-immunologic crosstalk and our preclinical data showing synergistic CRC growth suppression with the SGLT-2 inhibitor canagliflozin plus PD-1 blockade. This phase II trial investigates the safety and efficacy of canagliflozin-tislelizumab combination in metastatic MSI-H CRC, evaluating its impact on PFS, OS, and ORR while dissecting tumor microenvironment modulation mechanisms, thereby pioneering a novel metabolic-immunotherapy paradigm that could redefine treatment paradigms through dual metabolic-immune regulation.

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Extracted eligibility criteria

Cancer type

Colorectal Cancer

Biomarker criteria

Required: BRAF wild-type

Required: KRAS wild-type

Required: NRAS wild-type

Excluded: BRAF v600e

Disease stage

Metastatic disease required

Patients with unresectable locally advanced, recurrent, or distant metastatic colorectal cancer

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

Min 2 prior lines

Must have received: standard treatment

Patients who have experienced disease progression after receiving at least two lines of standard treatment, or who cannot tolerate the toxic side effects

Cannot have received: SGLT2 inhibitor (dapagliflozin, empagliflozin, canagliflozin)

Previous treatment with SGLT2 inhibitors (such as dapagliflozin, empagliflozin, canagliflozin)

Lab requirements

Blood counts

Hemoglobin ≥80 g/L; neutrophil count >1.5×10⁹/L; platelet count ≥90×10⁹/L

Kidney function

serum creatinine ≤1.5×ULN or creatinine clearance rate ≥50 mL/min (Cockcroft-Gault formula); eGFR ≥60 mL/min/1.73 m²

Liver function

Total bilirubin ≤1.5×ULN; ALT or AST ≤2.5×ULN

Cardiac function

LVEF ≥50%

Good function of major organs, that is, the relevant examination indicators within 14 days before randomization meet the following requirements (without blood or blood product transfusion, without the use of hematopoietic stimulating factors, and without the use of albumin or blood products): Routine blood test: Hemoglobin ≥80 g/L; neutrophil count >1.5×10⁹/L; platelet count ≥90×10⁹/L. Biochemical test: Total bilirubin ≤1.5×ULN (upper limit of normal value); serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; serum creatinine (SCr) ≤1.5×ULN or creatinine clearance rate ≥50 mL/min (Cockcroft-Gault formula). Prothrombin time (PT), international normalized ratio (INR) ≤1.5×ULN (unless warfarin anticoagulation is being used). Cardiac Doppler ultrasound evaluation: Left ventricular ejection fraction (LVEF) ≥50%. Renal function: eGFR ≥60 mL/min/1.73 m². Blood glucose: HbA1c ≤9%.

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