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

Официальное название

A Prospective Single-arm Phase Ib/II Study on the Safety and Efficacy of Fruquintinib Plus Chidamide and Sintilimab in the Third and Later Line Treatment of MSS/pMMR Metastatic Colorectal Cancer

Обзор

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.

Вмешательства

• Препарат Fruquintinib
  Fruquintinib: 5mg qd, po, 2 weeks on/1 week off, q3w, or 3mg qd, po, q3w.
• Препарат Sintilimab
  Sintilimab: 200mg, iv, d1, q3w.
• Препарат Chidamide
  Chidamide: 30mg/m2, po, biw.

Первичные конечные точки

• Progress-free Survival(PFS) [Срок оценки: 24 months]

Вторичные конечные точки (4)

• Objective response rate (ORR) [Срок оценки: 24 months]
• Overall Survival (OS) [Срок оценки: 24 months]
• Disease control rate (DCR) [Срок оценки: 24 months]
• Duration of response (DoR) [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Fully understand this study and voluntarily sign the informed consent form;
• Age between 18-75 years inclusive;
• Patients with histologically confirmed unresectable locally advanced, recurrent, or metastatic colorectal adenocarcinoma;
• Failure of standard second-line systemic treatment with measurable lesions;
• 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);
• ECOG performance status of 0-2, with no deterioration within 7 days;
• BMI≥18;
• Expected survival ≥3 months;
• 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.
• Women of childbearing age must use effective contraception;
• Good compliance and cooperation with follow-up.

Критерии исключения

• Unable to comply with the study protocol or procedures;
• Pregnant or breastfeeding women;
• Concurrent with any of the following conditions: uncontrolled hypertension, coronary artery disease, arrhythmias, and heart failure;
• Previous treatment with small molecule tyrosine kinase inhibitors for metastatic disease;
• Previous treatment with romidepsin;
• Previous treatment with immune checkpoint inhibitors for metastatic disease;
• Uncontrollable severe concurrent infections;
• Acute myocardial infarction, acute coronary syndrome, or CABG within 3 months before the first treatment;
• Subjects allergic to the study medication or any of its excipients;
• Known human immunodeficiency virus (HIV) infection. Known clinically significant liver disease history, including viral hepatitis \[known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (>1×10\^4 copies/mL or >2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (>1×10\^3 copies/mL)\];

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China PLAGH — Пекин

Идентификаторы

NCT: NCT06685276 · 2024-415

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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