Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer

Dai, Guanghai

Status and phase: Enrolling; Phase 2

Conditions: Colorectal Cancer Metastatic

Treatments: Drug: Sintilimab; Drug: Chidamide; Drug: Fruquintinib

Study type: Interventional

Funder types: Other

Identifiers

NCT06685276

2024-415

Details and patient eligibility

About

The prognosis of most patients with unresectable locally advanced or metastatic colorectal cancer (CRC) remains poor despite the advancements in chemotherapy and target therapy.

CAPability-01 trial investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer.

Based on the previous findings of CAPability-01, we will further evaluate the efficacy and safety of sintilimab and chidamide in combination with fruquintinib in the same setting.

Enrollment: 46 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Fully understand this study and voluntarily sign the informed consent form;

2. Age between 18-75 years inclusive;

3. Patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma;

4. Failure of standard second-line systemic treatment with measurable lesions;

5. Tumor tissue tested for microsatellite stability (MSS) or low microsatellite instability (MSI-L) by PCR, or confirmed pMMR by immunohistochemistry for DNA mismatch repair (MMR) protein (including MLH1, MSH2, MSH6, and PMS2 protein expression);

6. ECOG performance status of 0-2, with no deterioration within 7 days;

7. BMI≥18;

8. Expected survival ≥3 months;

9. Major organ functions meet the following requirements (no use of any blood components and growth factors within 14 days before enrollment):

   • Absolute neutrophil count ≥1.5×109/L, white blood cells ≥4.0×109/L;
   • Platelets ≥100×109/L;
   • Hemoglobin ≥90g/L;
   • Total bilirubin TBIL ≤1.5 times ULN;
   • ALT and AST ≤5 times ULN;
   • Urea/BUN and creatinine (Cr) ≤1.5×ULN (and creatinine clearance (CCr) ≥ 50mL/min);
   • Left ventricular ejection fraction (LVEF) ≥50%;
   • Corrected QT interval by Fridericia's formula (QTcF) <470 milliseconds.
   • INR ≤1.5×ULN, APTT ≤1.5×ULN.

10. Women of childbearing age must use effective contraception;

11. Good compliance and cooperation with follow-up.

Exclusion criteria

1. Unable to comply with the study protocol or procedures;

2. Pregnant or breastfeeding women;

3. Concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure;

4. Previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease;

5. Previous treatment with romidepsin;

6. Previous treatment with immune checkpoint inhibitors for metastatic disease;

7. Uncontrollable severe concurrent infections;

8. Acute myocardial infarction, acute coronary syndrome, or CABG within 3 months before the first treatment;

9. Subjects allergic to the study medication or any of its excipients;

10. Known human immunodeficiency virus (HIV) infection. Known clinically significant liver disease history, including viral hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×10^4 copies/mL or >2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (>1×10^3 copies/mL)];

11. Patients whom the investigator deems inappropriate for inclusion in this study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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46 participants in 1 patient group

Study arm

Experimental group

Description:

Fruquintinib Sintilimab Chidamide Treatments are administered until disease progression or toxicity intolerable.

Treatment:

Drug: Fruquintinib

Drug: Chidamide

Drug: Sintilimab