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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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)
• Препарат 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)
• Препарат 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)

Первичные конечные точки

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

Вторичные конечные точки (4)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07007767 · UHCT-CRC-240601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗