Immunotheray Combined With Simvastatin and Target Therapy and Chemotharepy for Advanced Colorectal Cancer

Официальное название

A Multicenter, Prospective, Phase II Exploratory Study on the First-line Treatment of MSS/ PMMR-type Advanced Colorectal Cancer With Adebrelimab Combined With Simvastatin and Targeted and Chemotherapy

Обзор

Metastatic colorectal cancer with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) molecular phenotypes could significantly benefit from immune checkpoint inhibitor therapy, ushering in the MSI era of immunotherapy for colorectal cancer. However, MSI-H/dMMR is present in only 15%-20% of stage II/III and 5% of stage IV colorectal cancer patients, while the vast majority of patients exhibit microsatellite stability (MSS) or proficient mismatch repair (pMMR) types, which are insensitive to immunotherapy. Therefore, how to enhance the efficacy of immunotherapy in the pMMR/MSS population through combination therapy has become a hotspot and challenge in colorectal cancer research.

Вмешательства

• Препарат Adebrelimab
  Adebrelimab\[1200mg i.v, q3w\], Capecitabine \[1000mg/m² po, bid, d1-d14, q3w\], Oxaliplatin \[130mg/m² i.v, d1, q3w\], Bevacizumab \[7.5mg/kg i.v, d1, q3w\], Simvastatin \[80mg po qd\] regimen treatment, 6-8 weeks, then enter the maintenance phase, with oxaliplatin discontinued during the maintenance phase

Первичные конечные точки

• Investigator-assessed Objective Response Rate（ORR） [Срок оценки: 2 years.]

Вторичные конечные точки (4)

• Overall Survival(OS) [Срок оценки: up to 5 years after treatment discontinuation]
• Progression Free Survival(PFS) [Срок оценки: From treatment initiation until documented disease progression, death, or up to 1 years of follow-up, with survival follow-up conducted every 3 months (±14 days) via telephone after treatment discontinuation.]
• Disease Control Rate(DCR) [Срок оценки: Imaging examinations will be performed every 6 weeks for the first 12 months after initial treatment, then every 12 weeks thereafter through study completion (maximum follow-up of 1 years).]
• Safety (Adverse Events, Vital Signs, Laboratory Parameters, and Quality of Life Assessed Using NCI-CTCAE v5.0) [Срок оценки: From ICF through 100 days after the last dose of study treatment]

Критерии участия

Критерии включения

• Able to provide written informed consent and voluntarily participate in this study.
• Male or female subjects aged between 18 and 75 years, inclusive.
• Histologically or cytologically confirmed metastatic colorectal adenocarcinoma.
• No prior systemic anti-tumor therapy; patients who have received neoadjuvant/adjuvant therapy are eligible if the time from the last chemotherapy to recurrence or progression is more than 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of at least 3 months.
• Presence of at least one measurable lesion at baseline assessed by the investigator according to RECIST 1.1. Measurable lesions must not have been previously treated with radiotherapy or other local therapy, unless the lesion located in a previously irradiated area has been confirmed to have progressed.
• Adequate organ function as defined below (no blood products or hematopoietic growth factors are allowed within 14 days prior to the first dose of study treatment):

• Absolute neutrophil count (ANC) ≥1.5×10\^9/L
• Platelet count ≥100×10\^9/L
• Hemoglobin ≥9 g/dL
• Serum albumin ≥2.5 g/dL
• Total bilirubin ≤1.5 × ULN; ALT and AST ≤2.5 × ULN, or ≤5 × ULN in the presence of liver metastases
• Serum creatinine ≤1.5 × ULN, or creatinine clearance >60 mL/min (calculated by Cockcroft-Gault formula)
• Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤1.5 × ULN. Subjects receiving stable-dose anticoagulation such as low molecular weight heparin or warfarin with INR within the expected therapeutic range are eligible.
• Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment, must not be breastfeeding, and must agree to use effective contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study and for at least 6 months after the last dose of study treatment. Male subjects with partners of childbearing potential must be surgically sterile or agree to use effective contraception during the study and for 3 months after the last dose of study treatment, and must not donate sperm during the study period.

Критерии исключения

• Received local radiotherapy within 4 weeks prior to the first dose of study drug, and adverse events due to radiotherapy have not recovered to baseline levels. Subjects who received palliative radiotherapy to peripheral sites (e.g., bone metastases) more than 4 weeks prior to the first dose are eligible, provided they have recovered from any acute adverse reactions.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have stable brain metastases and have not required steroid treatment for brain metastases for at least 28 days prior to study entry. This exception does not apply to carcinomatous meningitis, which is excluded regardless of clinical stability.
• Major surgery, open biopsy, or severe trauma within 28 days prior to the first dose of study drug.
• History of allergy to any anti-angiogenic agents, any component of monoclonal antibodies, capecitabine, oxaliplatin, or other platinum-based drugs.
• Uncontrolled hypertension despite anti-hypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
• Subjects with uncontrolled cardiovascular clinical symptoms or diseases, including but not limited to: (1) NYHA class II or higher heart failure; (2) unstable angina pectoris; (3) myocardial infarction within the past 1 year; (4) clinically significant supraventricular or ventricular arrhythmias without clinical intervention or still poorly controlled after clinical intervention.
• Significant clinically relevant bleeding symptoms or clear bleeding tendency within 3 months prior to the first dose, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or vasculitis.
• Arterial/venous thromboembolic events within 6 months prior to the first dose, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism. Superficial venous thrombosis may be included at the investigator's discretion.
• Presence of another progressing or actively treated malignancy, except for non-melanoma skin cancer and cervical carcinoma in situ that have received curative treatment.
• Subjects with other factors that, in the investigator's opinion, may lead to premature discontinuation of the study, such as other severe diseases (including psychiatric disorders) requiring concomitant treatment, clinically significant laboratory abnormalities, family or social factors that may affect subject safety or trial data collection.

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

Китай · 2 центра

• Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University) — Нанкин
• Nanjing First Hospital, Nanjing Medical University Affiliated Hospital — Нанкин

Идентификаторы

NCT: NCT07718490 · 2025-SR-692.A2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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