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

NCT07009145 | Not Yet Recruiting Phase 2

• 1 other identifier: YXLL-KY-2025(092)
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

QL1706; CRC; MSI-H/dMMR

Outcome Measures

Primary Outcomes (1)

• ORR

  The proportion of subjects with complete response (CR) and partial response (PR) according RESIST1.1 in total subjects

  approximately 6 months after the last subject participating in

Secondary Outcomes (7)

• DCR

  approximately 12 months after the last subject participating in

• DOR

  approximately 12 months after the last subject participating in

• PFS

  approximately 12 months after the last subject participating in

• 6/12/24 PFS rate

  6/12/24 months after the last subject participating in

• OS

  approximately 12 months after the last subject participating in

Study Arms (1)

QL1706 + Bevacizumab

EXPERIMENTAL

Drug: QL1706; Drug: Bevacizumab

Interventions

QL1706 DRUG

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).

QL1706 + Bevacizumab

Bevacizumab DRUG

Bevacizumab is administered at a dose of 7.5 mg/kg every 3 weeks (Q3W) via intravenous (iv) infusion.

QL1706 + Bevacizumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Qianfoshan Hospital: lead
• Linyi Tumour Hospital: collaborator
• Shandong Provincial Hospital: collaborator
• Qingdao Central Hospital: collaborator

Study Sites (1)

The First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, 250000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jun Wang, Associate Director, Department of Oncology, MD, PHD

CONTACT

0531-82169851; ggjun2005@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Department of Oncology

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 6, 2025
• Study Start: June 27, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 6, 2025

Record last verified: 2025-05

Locations

CN (1)