ql1706 plus bevacizumab for unresectable or metastatic msi-h/dmmr crc

Conditions: Unresectable Colorectal Cancer; Metastatic Colorectal Cancer (CRC); MSI-H/dMMR Colorectal Cancer

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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. exclusion criteria: * 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.

Keywords: ql1706 crc msi-h/dmmr