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

NCT06685276 | Recruiting Phase 2

• 1 other identifier: 2024-415
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Progress-free Survival(PFS)

  The time from enrollment until tumor progression or death from any cause, whichever occurred first

  24 months

Secondary Outcomes (4)

• Objective response rate (ORR)

  24 months

• Overall Survival (OS)

  24 months

• Disease control rate (DCR)

  24 months

• Duration of response (DoR)

  24 months

Study Arms (1)

Study arm

EXPERIMENTAL

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

Drug: Fruquintinib; Drug: Sintilimab; Drug: Chidamide

Interventions

Fruquintinib DRUG

Fruquintinib: 5mg qd, po, 2 weeks on/1 week off, q3w, or 3mg qd, po, q3w.

Also known as: hmpl-013

Study arm

Sintilimab DRUG

Sintilimab: 200mg, iv, d1, q3w.

Study arm

Chidamide DRUG

Chidamide: 30mg/m2, po, biw.

Study arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);

You may not qualify if:

• 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 \[known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e., HBV DNA positive (\>1×10\^4 copies/mL or \>2000 IU/mL); known hepatitis C virus (HCV) infection and HCV RNA positive (\>1×10\^3 copies/mL)\];

Sponsors & Collaborators

• Dai, Guanghai: lead

Study Sites (1)

China PLAGH

Beijing, China

RECRUITING

MeSH Terms

Interventions

HMPL-013; sintilimab; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 12, 2024
• Study Start: August 16, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

CN (1)