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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Fruquintinib; Drug: Sintilimab; Drug: Chidamide

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • China PLAGH
    • Contact: Guanghai Dai, M.D.; Phone Number: 13801232381; Email: daigh301@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)];

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study arm; Fruquintinib Sintilimab Chidamide Treatments are administered until disease progression or toxicity intolerable.	Drug: Fruquintinib; Fruquintinib: 5mg qd, po, 2 weeks on/1 week off, q3w, or 3mg qd, po, q3w.; Other Names: hmpl-013; Drug: Sintilimab; Sintilimab: 200mg, iv, d1, q3w.; Drug: Chidamide; Chidamide: 30mg/m2, po, biw.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress-free Survival(PFS)	The time from enrollment until tumor progression or death from any cause, whichever occurred first	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of patients with a PR or CR	24 months
Overall Survival (OS)	The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date	24 months
Disease control rate (DCR)	The proportion of patients with a PR, CR, or SD	24 months
Duration of response (DoR)	For patients who achieved a complete response (CR) or partial response (PR), the time from the first tumor assessment demonstrating response until disease progression or death, whichever occurred first	24 months

Collaborators and Investigators

• Sponsor: Dai, Guanghai

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 11, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 17, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2024-415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No