Clinical trial NCT07009145: QL1706 Plus Bevacizumab for Unresectable or Metastatic MSI-H/dMMR CRC
Official title: An Exploratory Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Bevacizumab for the Treatment of Unresectable or Metastatic MSI-H/dMMR Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Unresectable Colorectal Cancer
Metastatic Colorectal Cancer (CRC)
MSI-H/dMMR Colorectal Cancer
Keywords: QL1706
CRC
MSI-H/dMMR
Lead sponsor: Qianfoshan Hospital
Sponsor class: OTHER
Collaborators: name: Linyi Tumour Hospital
name: Shandong Provincial Hospital
name: Qingdao Central Hospital
First posted: 2025-06-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: ORR
timeFrame: approximately 6 months after the last subject participating in
Secondary outcomes:
measure: DCR
timeFrame: approximately 12 months after the last subject participating in
measure: DOR
timeFrame: approximately 12 months after the last subject participating in
measure: PFS
timeFrame: approximately 12 months after the last subject participating in
measure: 6/12/24 PFS rate
timeFrame: 6/12/24 months after the last subject participating in
measure: OS
timeFrame: approximately 12 months after the last subject participating in
measure: 6/12/24 OS rate
timeFrame: 6/12/24 months after the last subject participating in
measure: Safety (adverse event)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Jinan
country: China
facility: The First Affiliated Hospital of Shandong First Medical University
state: Shandong
Study officials:
References: