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

Official title

An Open-label, Single-arm, Exploratory Study of Sintilimab in Combination With Bevacizumab and Decitabine for the Treatment of Advanced pMMR/MSS Colorectal Cancer in Third-line or Later Settings

Overview

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.

Interventions

• Drug 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)
• 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)
• 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)

Primary outcome measures

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator Assessment [Time frame: every 12 weeks (±7 days) up to 2 years]

Secondary outcome measures (4)

• Overall Survival (OS) [Time frame: every 12 weeks (±7 days) up to 2 years]
• Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator Assessment [Time frame: every 12 weeks (±7 days) up to 2 years]
• Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator Assessment [Time frame: every 12 weeks (±7 days) up to 2 years]
• Number of Participants Who Experienced an Adverse Event (AE) [Time frame: Serious AEs: Up to 90 days after last dose of study treatment; Other AEs: Up to 30 days after last dose of study treatment]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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).
• HIV infection (HIV 1/2 antibody-positive).
• Untreated active hepatitis B (HBsAg-positive with HBV-DNA exceeding the upper limit of normal).
• Pregnancy or lactation.
• Severe or uncontrolled systemic diseases.
• Any condition (medical, psychiatric, laboratory abnormality, or logistical) that, in the investigator's judgment, compromises patient safety, data integrity, or protocol compliance.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07007767 · UHCT-CRC-240601

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗