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

A Randomized Phase 2 Clinical Trial Evaluating Sintilimab and Chidamide in Combination With or Without IBI305 in Patients With Standard Treatment Failure of Advanced or Metastatic pMMR/MSS Colorectal Carcinoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Microsatellite Stable Colorectal Cancer; Metastatic Microsatellite-stable Colorectal Cancer
• Intervention / Treatment: Drug: Sintilimab; Drug: Chidamide; Drug: IBI305

Detailed Description

In this study, we explored the potential effectiveness of combining PD-1 monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide, with or without IBI305(bevacizumab), in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. Fourty-eight patients were randomized into two groups: the doublet group, who received sintilimab 200 mg every 3 weeks and chidamide 30 mg orally twice weekly, and the triplet group, who received sintilimab, chidamide, and bevacizumab 7.5 mg/kg every 3 weeks.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Feng Wang, MD, PhD; Phone Number: 86-20-87343795; Email: wangfeng@sysucc.org.cn
• Study Contact Backup: Name: Ruihua Xu, MD, PhD; Phone Number: 86-20-87343333; Email: xuruihua@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer center of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
2. Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
3. Subjects must have failed at least two lines of prior treatment.
4. Subjects must have one measurable lesion according to RECIST v1.1 at least.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. 18-75 years old.
7. Life expectancy of at least 12 weeks.
8. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol

Exclusion Criteria:

1. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or histone deacetylase (HDAC) inhibitor.
2. 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.
3. Received radiotherapy with 4 weeks of the first dose of study medication.
4. Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
5. 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.
6. Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
7. Interstitial lung disease requiring corticosteroids.
8. Active or poorly controlled serious infections.
9. Significant malnutrition.
10. Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
11. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
12. 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.
13. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
14. Any life-threatening bleeding within 3 months prior to the enrollment.
15. High risk of bleeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The triplet group (sintilimab + chidamide + IBI305); 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; 200mg IV on Day 1 Q3W; Drug: Chidamide; 30mg PO BIW each 3-week cycle; Drug: IBI305; 7.5mg/kg IV on Day 1 Q3W; Other Names: Bevacizumab
Active Comparator: The doublet group (sintilimab + chidamide); Every 3 weeks, patients received sintilimab 200 mg on day one and chidamide 30 mg orally twice weekly.	Drug: Sintilimab; 200mg IV on Day 1 Q3W; Drug: Chidamide; 30mg PO BIW each 3-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of patients with a PR or CR	2 year
Progression-free survival (PFS);	The time from enrollment until tumor progression or death from any cause, whichever occurred first	2 year
Overall Survival (OS);	The time calculated from enrollment until death from any cause, with living patients censored at the last known survival date	2 year
Disease control rate (DCR)	The proportion of patients with a PR, CR, or SD	2 year
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	2 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Ruihua Xu, MD, PhD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2021
• Primary Completion (Actual): July 26, 2022
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal Carcinoma, pMMR, Microsatellite-stable
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: CAPability-01

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