Sintilimab and Chidamide in Combination With or Without IBI305 in Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

NCT04724239 | Unknown Phase 2

• 1 other identifier: CAPability-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of sintilimab and chidamide in combination with or without IBI305(bevacizumab) in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.

Conditions

Advanced Microsatellite Stable Colorectal Cancer; Metastatic Microsatellite-stable Colorectal Cancer

Keywords

Colorectal Carcinoma, pMMR, Microsatellite-stable

Outcome Measures

Primary Outcomes (1)

• The progression-free survival (PFS) rates at 18 weeks

  The proportion of patients without disease progression or death at the 18th week after initiation of the study treatment

  24 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  2 year

• Progression-free survival (PFS);

  2 year

• Overall Survival (OS);

  2 year

• Disease control rate (DCR)

  2 year

• Duration of response (DoR)

  2 year

Study Arms (2)

The triplet group (sintilimab + chidamide + IBI305)

EXPERIMENTAL

Every 3 weeks, patients received sintilimab 200 mg and IBI305(bevacizumab) 7.5 mg/kg on day one and chidamide 30 mg orally twice weekly.

Drug: Sintilimab; Drug: Chidamide; Drug: IBI305

The doublet group (sintilimab + chidamide)

ACTIVE COMPARATOR

Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.

Drug: Sintilimab; Drug: Chidamide

Interventions

Sintilimab DRUG

200mg IV on Day 1 Q3W

The doublet group (sintilimab + chidamide); The triplet group (sintilimab + chidamide + IBI305)

Chidamide DRUG

30mg PO BIW each 3-week cycle

The doublet group (sintilimab + chidamide); The triplet group (sintilimab + chidamide + IBI305)

IBI305 DRUG

7.5mg/kg IV on Day 1 Q3W

Also known as: Bevacizumab

The triplet group (sintilimab + chidamide + IBI305)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
• Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
• Subjects must have failed at least two lines of prior treatment.
• Subjects must have one measurable lesion according to RECIST v1.1 at least.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• years old.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

You may not qualify if:

• Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or histone deacetylase (HDAC) inhibitor.
• Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.
• Received radiotherapy with 4 weeks of the first dose of study medication.
• Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
• Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.
• Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
• Interstitial lung disease requiring corticosteroids.
• Active or poorly controlled serious infections.
• Significant malnutrition.
• Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
• Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
• Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.
• History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
• Any life-threatening bleeding within 3 months prior to the enrollment.
• High risk of bleeding.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Cancer center of Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Wang F, Jin Y, Wang M, Luo HY, Fang WJ, Wang YN, Chen YX, Huang RJ, Guan WL, Li JB, Li YH, Wang FH, Hu XH, Zhang YQ, Qiu MZ, Liu LL, Wang ZX, Ren C, Wang DS, Zhang DS, Wang ZQ, Liao WT, Tian L, Zhao Q, Xu RH. Combined anti-PD-1, HDAC inhibitor and anti-VEGF for MSS/pMMR colorectal cancer: a randomized phase 2 trial. Nat Med. 2024 Apr;30(4):1035-1043. doi: 10.1038/s41591-024-02813-1. Epub 2024 Mar 4.

  PMID: 38438735 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ruihua Xu, MD, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The president of Sun Yat-sen University Cancer Center

Model Details: Subjects will be randomized in approximately a 1:1 ratio to receive sintilimab and chidamide with or without IBI305.

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 26, 2021
• Study Start: March 11, 2021
• Primary Completion: July 26, 2022
• Study Completion: December 1, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

CN (1)