QL1706 Plus Bevacizumab for Unresectable or Metastatic MSI-H/dMMR CRC

Официальное название

An Exploratory Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Bevacizumab for the Treatment of Unresectable or Metastatic MSI-H/dMMR Colorectal Cancer

Обзор

This is a single-arm, multi-center, exploratory study evaluating the efficacy and safety of iparomlimab and tuvonralimab (QL1706) in combination with bevacizumab for the treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) unresectable or metastatic colorectal cancer. Eligible participants who meet the inclusion and exclusion criteria will provide written informed consent and receive QL1706 at 5.0 mg/kg and bevacizumab at 7.5 mg/kg on Day 1 of every 3-week cycle (Q3W), until disease progression or completion of 2 years of treatment. The primary endpoint of this study is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), PFS and OS rates at 6, 12, and 24 months, and safety.

Вмешательства

• Препарат QL1706
  QL1706 (Iparomlimab and Tuvonralimab) is administered at a dose of 5 mg/kg via intravenous infusion on Day 1 of each 3-week cycle (Q3W).
• Препарат Bevacizumab
  Bevacizumab is administered at a dose of 7.5 mg/kg every 3 weeks (Q3W) via intravenous (iv) infusion.

Первичные конечные точки

• ORR [Срок оценки: approximately 6 months after the last subject participating in]

Вторичные конечные точки (7)

• DCR [Срок оценки: approximately 12 months after the last subject participating in]
• DOR [Срок оценки: approximately 12 months after the last subject participating in]
• PFS [Срок оценки: approximately 12 months after the last subject participating in]
• 6/12/24 PFS rate [Срок оценки: 6/12/24 months after the last subject participating in]
• OS [Срок оценки: approximately 12 months after the last subject participating in]
• 6/12/24 OS rate [Срок оценки: 6/12/24 months after the last subject participating in]
• Safety (adverse event) [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• Voluntarily signs the informed consent form.
• Aged between 18 and 80 years (inclusive) at the time of consent; no gender restriction.
• Histologically confirmed unresectable locally advanced or metastatic colorectal cancer.
• At least one measurable target lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior immunotherapy for unresectable locally advanced or metastatic colorectal cancer.
• If previously treated with standard neoadjuvant or adjuvant therapy, the interval from the last dose to the first study treatment must be ≥ 6 months.
• Willing and able to provide tumor tissue and blood samples for MSI, RAS, BRAF, and PD-L1 testing.
• Estimated life expectancy of ≥ 12 months.
• Appropriate laboratory values must be met at screening.
• Female participants must be non-lactating, and have a negative pregnancy test result prior to enrollment.
• Participants of childbearing potential must agree to use effective contraception from the time of informed consent until at least 180 days after the last dose of study treatment.

Критерии исключения

• Known history of severe allergic reactions to iparomlimab and tuvonralimab or bevacizumab.
• Active malignancy other than colorectal cancer within 5 years prior to first treatment.
• Large tumor lesions, especially those previously irradiated, with signs of bleeding.
• Imaging showing tumor invasion of major blood vessels (e.g., pulmonary artery or superior vena cava), including encasement or invasion of the vessel lumen.
• Brain metastases (asymptomatic or treated symptomatic brain metastases stable for >4 weeks allowed).
• Active autoimmune disease requiring systemic treatment.
• Active pulmonary diseases such as tuberculosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction during screening.
• Requirement for long-term or high-dose NSAIDs (aspirin >325 mg) or anticoagulant therapy.
• History of severe gastrointestinal events within 6 months prior to first treatment.
• Severe intestinal obstruction symptoms or signs and unretrieved intestinal stents at screening.
• Cardiovascular or cerebrovascular diseases including but not limited to: NYHA class > II heart failure; unstable or severe angina; myocardial infarction or stroke within 6 months; atrial fibrillation or other arrhythmias requiring treatment; symptomatic superior vena cava syndrome; prolonged QT interval (male QT > 450 ms; female QTc > 470 ms); uncontrolled hypertension despite medication (SBP >140 mmHg and/or DBP >90 mmHg) or history of hypertensive crisis or encephalopathy.
• Known bleeding disorders or coagulopathies.
• Uncontrolled pleural, pericardial, or ascitic effusions requiring drainage.
• Active infection or unexplained fever >38.5°C at screening (cancer-related fever allowed).
• Use of systemic broad-spectrum antibiotics within 30 days prior to first treatment.
• Systemic corticosteroids (>10 mg prednisone equivalent daily) or immunosuppressants within 14 days prior to first treatment, or immunostimulants within 4 weeks.
• Major surgery, severe fractures, or therapeutic clinical trials within 4 weeks prior to first treatment; herbal treatment within 2 weeks.
• Ongoing adverse events from prior antitumor therapy greater than grade 1.
• HIV infection, other congenital or acquired immunodeficiencies, or history of organ or allogeneic bone marrow transplantation (except corneal transplantation).
• Positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with HBV DNA >10⁴ copies/mL (\~2000 IU/mL); or positive hepatitis C antibody with HCV RNA >10³ copies/mL; co-infection with HBV and HCV excluded.
• Vaccination with live or attenuated vaccines within 30 days prior to first treatment.
• Prior treatment with immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-OX-40, anti-CD137).
• Prior adjuvant targeted therapy against EGFR, VEGF, or VEGFR (e.g., bevacizumab, cetuximab, panitumumab, apatinib, regorafenib, anlotinib).
• Psychiatric disorders, epilepsy, dementia, or substance abuse that may affect compliance.
• Other conditions or lab abnormalities that may interfere with study participation or confound results as judged by investigators or sponsors.

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 · 1 центр

• The First Affiliated Hospital of Shandong First Medical University — Цзинань

Идентификаторы

NCT: NCT07009145 · YXLL-KY-2025(092)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗