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

NCT07007767 | Not Yet Recruiting Phase 2

• 1 other identifier: UHCT-CRC-240601
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator Assessment

  PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented.

  every 12 weeks (±7 days) up to 2 years

Secondary Outcomes (4)

• Overall Survival (OS)

  every 12 weeks (±7 days) up to 2 years

• Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator Assessment

  every 12 weeks (±7 days) up to 2 years

• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator Assessment

  every 12 weeks (±7 days) up to 2 years

• Number of Participants Who Experienced an Adverse Event (AE)

  Serious AEs: Up to 90 days after last dose of study treatment; Other AEs: Up to 30 days after last dose of study treatment

Study Arms (1)

sintilimab+bevacizumab+decitabine

EXPERIMENTAL

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.

Drug: sintilimab; Drug: Bevacizumab Biosimilar; Drug: Decitabine

Interventions

sintilimab 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)

Also known as: IBI308

sintilimab+bevacizumab+decitabine

Bevacizumab Biosimilar 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)

Also known as: IBI305

sintilimab+bevacizumab+decitabine

Decitabine 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)

sintilimab+bevacizumab+decitabine

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent obtained prior to initiation of any trial-related procedures;
• Age ≥18 years;
• Histologically confirmed colorectal adenocarcinoma;
• Microsatellite stable (MSS), microsatellite instability-low (MSI-L), or proficient mismatch repair (pMMR) status;
• ECOG Performance Status (PS) score of 0-1;
• Documented disease progression following standard second-line systemic therapy (prior exposure to irinotecan, oxaliplatin, or fluorouracil-based regimens, with or without targeted therapy \[e.g., bevacizumab, cetuximab\]);
• Adequate organ and bone marrow function confirmed by laboratory parameters.
• Anticipated survival exceeding 3 months.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR).
• Current participation in interventional clinical trials or administration of investigational drugs/devices within 4 weeks prior to the first dose.
• 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).
• 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).
• Radiographic evidence of tumor invasion/encasement of major blood vessels or bleeding tendency assessed by investigators/radiologists.
• Major surgery within 4 weeks prior to the first dose (excluding biopsy) or anticipated major surgery during the study period.
• Non-healed wounds, ulcers, or fractures.
• Minor surgical procedures (requiring local anesthesia, e.g., central venous catheterization) within 48 hours prior to the first dose.
• 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.
• 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).
• Inherited bleeding diathesis, coagulation disorders, or history of thrombosis.
• History of allogeneic organ transplantation (excluding corneal transplants) or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to sintilimab, bevacizumab, decitabine, or their excipients.
• Inadequate recovery from prior intervention-related toxicities/complications (i.e., \>Grade 1 or not returned to baseline, excluding fatigue/alopecia).

Sponsors & Collaborators

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

MeSH Terms

Interventions

sintilimab; Decitabine

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Tao Zhang, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lei Zhao, Ph.D.

CONTACT

+86 13871132725; zhaolei8704@126.com

Tao Zhang, Ph.D.

CONTACT

+86-027-85871993; taozhangxh@hust.edu.cn;284409937@qq.com

Study Design

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

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: June 6, 2025
• Study Start: June 15, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: 2027/12/30
• Access Criteria: After the research findings are publicly published