Exploring Sintilimab + Bevacizumab + Decitabine for Advanced pMMR/MSS Colorectal Cancer (After 2+ Prior Therapies）

NCT ID: NCT07007767

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-15
• Study Completion Date: 2027-12-30

Brief Summary

This study investigates the efficacy and safety of sintilimab in combination with bevacizumab and decitabine for patients with advanced proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer who have undergone ≥3 prior lines of systemic therapy.

Participants will receive intravenous infusions of sintilimab, bevacizumab, and decitabine in 3-week treatment cycles until disease progression, intolerable toxicity, initiation of new antitumor therapy, withdrawal of informed consent, loss to follow-up, death, or investigator-determined discontinuation criteria (whichever occurs first). The maximum treatment duration for sintilimab is 24 months.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sintilimab+bevacizumab+decitabine

Subjects will receive Sintilimab (anti-PD-1 monoclonal antibody) in combination with Bevacizumab biosimilar（anti-VEGF monoclonal antibody) and Decitabine (hypomethylating agent) via intravenous infusion on a 3-week cycle (Q3W) until disease progression (PD), unacceptable toxicity, initiation of new antitumor therapy, withdrawal of informed consent, loss to follow-up, death, or investigator-determined discontinuation criteria (whichever occurs first).

The maximum treatment duration for Sintilimab is 24 months.

Group Type: EXPERIMENTAL

sintilimab

Intervention Type: DRUG

Sintilimab (anti-PD-1 monoclonal antibody) Specification: 100 mg/10 mL (10 mg/mL concentrated solution)

Administration:

Dose: 200 mg (fixed dose) Route: Intravenous (IV) infusion over 30-60 minutes Schedule: Day 1 of each 21-day cycle (Q3W)

Bevacizumab Biosimilar

Intervention Type: DRUG

Bevacizumab biosimilar (anti-VEGF monoclonal antibody) Specification: 100 mg/4 mL (25 mg/mL concentrated solution)

Administration:

Dose: 7.5 mg/kg (body weight-adjusted) Route: IV infusion Schedule: Day 1 of each 21-day cycle (Q3W)

Decitabine

Intervention Type: DRUG

Decitabine (hypomethylating agent) Specification: 10 mg lyophilized powder per vial

Administration:

Dose: 10 mg/m²/day (body surface area-adjusted) Route: IV infusion over 1 hour Schedule: Days 1-5 of each 21-day cycle (Q3W)

Interventions

sintilimab

Sintilimab (anti-PD-1 monoclonal antibody) Specification: 100 mg/10 mL (10 mg/mL concentrated solution)

Administration:

Dose: 200 mg (fixed dose) Route: Intravenous (IV) infusion over 30-60 minutes Schedule: Day 1 of each 21-day cycle (Q3W)

Intervention Type: DRUG

Bevacizumab Biosimilar

Bevacizumab biosimilar (anti-VEGF monoclonal antibody) Specification: 100 mg/4 mL (25 mg/mL concentrated solution)

Administration:

Dose: 7.5 mg/kg (body weight-adjusted) Route: IV infusion Schedule: Day 1 of each 21-day cycle (Q3W)

Intervention Type: DRUG

Decitabine

Decitabine (hypomethylating agent) Specification: 10 mg lyophilized powder per vial

Administration:

Dose: 10 mg/m²/day (body surface area-adjusted) Route: IV infusion over 1 hour Schedule: Days 1-5 of each 21-day cycle (Q3W)

Intervention Type: DRUG

Other Intervention Names

IBI308; IBI305

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent obtained prior to initiation of any trial-related procedures;

2. Age ≥18 years;

3. Histologically confirmed colorectal adenocarcinoma;

4. Microsatellite stable (MSS), microsatellite instability-low (MSI-L), or proficient mismatch repair (pMMR) status;

5. ECOG Performance Status (PS) score of 0-1;

6. Documented disease progression following standard second-line systemic therapy (prior exposure to irinotecan, oxaliplatin, or fluorouracil-based regimens, with or without targeted therapy [e.g., bevacizumab, cetuximab]);

7. Adequate organ and bone marrow function confirmed by laboratory parameters.

8. Anticipated survival exceeding 3 months.

9. For females of childbearing potential, a negative urine or serum pregnancy test must be confirmed within 3 days prior to the first dose of study drug (Cycle 1 Day 1). Serum pregnancy testing is required if urine results are inconclusive. Non-childbearing potential is defined as ≥1 year postmenopausal, surgically sterilized (bilateral oophorectomy or hysterectomy), or confirmed premature ovarian failure.

10. All subjects at risk of conception must employ highly effective contraception (failure rate <1% per year) throughout the treatment period and for 120 days after the last dose of study drug.

11. Subjects must consent to provide sufficient tumor tissue specimens for PD-L1 expression analysis, including archived samples (paraffin-embedded blocks or unstained sections meeting protocol-specified requirements). If archived tissue is unavailable, subjects must agree to undergo re-biopsy of the tumor lesion.

Exclusion Criteria

1. Other malignancies diagnosed within the past 5 years, excluding radically resected basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.

2. Microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR).

3. Current participation in interventional clinical trials or administration of investigational drugs/devices within 4 weeks prior to the first dose.

4. Prior therapy with anti-PD-1/PD-L1/PD-L2 agents or drugs targeting stimulatory/coinhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137).

5. Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Exemptions: Replacement therapy (e.g., thyroxine, insulin, or physiologic glucocorticoids for adrenal/pituitary insufficiency).

6. Radiographic evidence of tumor invasion/encasement of major blood vessels or bleeding tendency assessed by investigators/radiologists.

7. Major surgery within 4 weeks prior to the first dose (excluding biopsy) or anticipated major surgery during the study period.

8. Non-healed wounds, ulcers, or fractures.

9. Minor surgical procedures (requiring local anesthesia, e.g., central venous catheterization) within 48 hours prior to the first dose.

10. Current or recent (within 10 days prior to the first dose) daily use of aspirin (>325 mg/day) or other NSAIDs with platelet-inhibiting effects.

11. Current or recent (within 10 days prior to the first dose) full-dose anticoagulants/thrombolytics (prophylactic low-dose anticoagulants permitted: ≤1 mg/day warfarin [INR ≤1.5], ≤12,000 U/day heparin, or ≤100 mg/day aspirin).

12. Inherited bleeding diathesis, coagulation disorders, or history of thrombosis.

13. History of allogeneic organ transplantation (excluding corneal transplants) or allogeneic hematopoietic stem cell transplantation.

14. Known hypersensitivity to sintilimab, bevacizumab, decitabine, or their excipients.

15. Inadequate recovery from prior intervention-related toxicities/complications (i.e., >Grade 1 or not returned to baseline, excluding fatigue/alopecia).

16. HIV infection (HIV 1/2 antibody-positive).

17. Untreated active hepatitis B (HBsAg-positive with HBV-DNA exceeding the upper limit of normal).

18. Pregnancy or lactation.

19. Severe or uncontrolled systemic diseases.

20. Any condition (medical, psychiatric, laboratory abnormality, or logistical) that, in the investigator's judgment, compromises patient safety, data integrity, or protocol compliance.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Tao Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tao Zhang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Central Contacts

Lei Zhao, Ph.D.

Role: CONTACT

zhaolei8704@126.com

+86 13871132725

Tao Zhang, Ph.D.

Role: CONTACT

taozhangxh@hust.edu.cn;284409937@qq.com

+86-027-85871993

Other Identifiers

UHCT-CRC-240601

Identifier Type: -

Identifier Source: org_study_id