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

Metastatic Microsatellite-stable Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04724239
• Other study ID #: CAPability-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 11, 2021
• Est. completion date: December 2023

Study information

• Verified date: July 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 2023
• Est. primary completion date: July 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Microsatellite Stable Colorectal Cancer
• Carcinoma
• Colorectal Neoplasms
• Metastatic Microsatellite-stable Colorectal Cancer

Intervention

Drug:
• Sintilimab
200mg IV on Day 1 Q3W
• Chidamide
30mg PO BIW each 3-week cycle
• IBI305
7.5mg/kg IV on Day 1 Q3W

Locations

Country	Name	City	State
China	Cancer center of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate (ORR)	The proportion of patients with a PR or CR	2 year
Secondary	Progression-free survival (PFS);	The time from enrollment until tumor progression or death from any cause, whichever occurred first	2 year
Secondary	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
Secondary	Disease control rate (DCR)	The proportion of patients with a PR, CR, or SD	2 year
Secondary	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