A Randomized, Open-Label, Controlled, Multicenter Phase III Clinical Study of SHR-A1811 in Combination With Chemotherapy and Bevacizumab Versus Standard Therapy as First-Line Treatment for Advanced Colorectal Cancer

Официальное название

A Randomized, Open-label, Controlled, Multicenter Phase III Clinical Study of SHR-A1811 in Combination With mFOLFOX6 (-1) and Bevacizumab Versus mFOLFOX6 in Combination With Bevacizumab as First-line Treatment for Advanced Colorectal Cancer.

Обзор

This study adopts a randomized, open-label, positive-controlled, multicenter design, aiming to evaluate the efficacy and safety of SHR-A1811 in combination with chemotherapy and bevacizumab versus standard therapy as first-line treatment for advanced colorectal cancer, and to explore the drug's immunogenicity and pharmacokinetic characteristics.

Вмешательства

• Препарат SHR-A1811, Oxaliplatin, Levo-leucovorin, Fluorouracil and Bevacizumab
  SHR-A1811 in combination with Oxaliplatin, Levo-leucovorin, Fluorouracil and Bevacizumab
• Препарат Oxaliplatin, Levo-leucovorin, Fluorouracil and Bevacizumab
  Oxaliplatin, Levo-leucovorin, Fluorouracil and Bevacizumab

Первичные конечные точки

• Progression-Free Survival (PFS) assessed by the Independent Review Committee (IRC) [Срок оценки: From the first dose to the last visit, approximately11 months]

Вторичные конечные точки (9)

• Objective Response Rate (ORR) assessed by Independent Review Committee (IRC) [Срок оценки: From the first dose to the last visit, approximately 11months]
• Duration of Response (DoR) assessed by Independent Review Committee (IRC) [Срок оценки: From the first dose to the last visit, approximately 11months]
• Progression-Free Survival (PFS) assessed by the Investigator [Срок оценки: From the first dose to the last visit, approximately11 months]
• Objective Response Rate (ORR) assessed by the Investigator [Срок оценки: From the first dose to the last visit, approximately 11 months]
• Duration of Response (DoR) assessed by the Investigator [Срок оценки: From the first dose to the last visit, approximately 11 months]
• Overall Survival (OS) [Срок оценки: From the first dose to the last visit, approximately 11 months]
• Incidence and severity of Adverse Events (AEs). [Срок оценки: From the first dose to the last visit, approximately11 months]
• Anti-SHR-A1811 Antibodies (ADA) [Срок оценки: From the first dose to the last visit, approximately 11 months]
• Plasma concentrations of toxin-conjugated antibody of SHR-A1811 [Срок оценки: From the first dose to the last visit, approximately 11 months]

Критерии участия

Критерии включения

• Subjects voluntarily enroll in the study, sign informed consent, demonstrate good compliance and cooperate with follow-up visits.
• Aged between 18 and 75 years inclusive, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Estimated survival expectancy ≥ 12 weeks.
• Histologically or cytologically confirmed colorectal adenocarcinoma.
• No prior systemic anti-tumor therapy.
• Tumor tissue specimen must be provided, either archived within 1 year prior to first study treatment or newly collected fresh specimen.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1; the measurable lesion shall not have received prior local therapy such as radiotherapy.
• Adequate organ function with relevant laboratory tests completed within 7 days before the first study treatment.
• Male subjects with fertile female partners and fertile female subjects must use highly effective contraception throughout the study. Fertile female subjects must have a negative serum or urine human chorionic gonadotropin (HCG) test within 7 days prior to first study drug administration and shall not be breastfeeding.

Критерии исключения

• Received systemic anti-tumor therapies (including investigational agents) or major surgery within 4 weeks prior to the first study drug administration; palliative radiotherapy within 2 weeks or surgery within 4 weeks before study treatment initiation.
• History of hypersensitivity to monoclonal antibodies or any component of the investigational products to be administered in this study.
• Pre-existing peripheral neuropathy of Grade >1.
• History of thromboembolic disease within 6 months or hemoptysis within 3 months before first study medication. Subjects with muscular venous thrombosis not requiring anticoagulation per investigator's assessment are eligible for enrollment.
• CT/MRI evidence of tumor encasement or invasion of major blood vessels.
• Non-gastrointestinal bleeding within 6 months prior to first study drug administration, or active peptic ulcer disease.
• Uncontrolled hypertension, or medical history of hypertensive crisis or hypertensive encephalopathy.
• History of severe cerebrovascular disease.
• Unresolved toxicities and/or complications from prior interventions that have not recovered to baseline.
• Subjects with a history of or current leptomeningeal metastases, or active brain metastases.
• Known or suspected interstitial lung disease (ILD); moderate-to-severe pulmonary disease significantly impairing respiratory function or autoimmune/connective tissue/inflammatory diseases involving the lung within 3 months before first dosing that may interfere with detection or management of drug-related pulmonary toxicity. Subjects who developed ≥Grade 3 ILD during prior immune checkpoint inhibitor treatment are excluded.
• Symptomatic moderate to severe ascites; uncontrolled moderate or greater pleural or pericardial effusion.
• Bowel obstruction within 3 months prior to first study treatment, or prior intestinal stent placement with the stent remaining in situ at screening.
• Uncontrolled or severe cardiovascular disease, or unstable angina/unstable arrhythmia occurring within 1 month before initiation of study treatment.
• Unexplained fever >38.5°C at screening or prior to first dose; severe infection (CTCAE Grade >2) within 4 weeks before study drug initiation; active pulmonary inflammation on baseline chest imaging, or clinical signs/symptoms of infection requiring oral or intravenous antibiotics within 2 weeks before first dosing.
• Previous or concurrent diagnosis of other malignant malignancies.
• Active hepatitis B or active hepatitis C infection.
• History of immunodeficiency including positive HIV test, congenital/acquired immunodeficiency disorders, or prior solid organ transplantation.
• Active pulmonary tuberculosis infection within 1 year prior to screening, or prior active pulmonary tuberculosis without standard anti-tuberculosis treatment even if diagnosed more than 1 year ago.
• Pregnant, breastfeeding females or females planning pregnancy during the study period.
• Uncontrolled psychiatric disorders, known alcohol abuse, illicit drug dependence, incarceration or other conditions that would preclude completion of study procedures.
• Any other conditions deemed inappropriate for study participation by the investigator, including clinically significant abnormal laboratory values, familial/social factors or other risks leading to premature study discontinuation or confounding study results.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing cancer Hospital — Пекин

Идентификаторы

NCT: NCT07676162 · SHR-A1811-317

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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