A Prospective, Single-Arm, Multicenter, Phase II Clinical Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Cetuximab and mFOLFIRI Regimen as First-Line Treatment for Recurrent or Metastatic Colorectal Cancer

1\. Radiotherapy or surgery within 30 days before initiation of study treatment (except prior diagnostic biopsy).

2\. Prior adjuvant chemotherapy for colorectal cancer (CRC), with an interval of less than 12 months between the end of adjuvant chemotherapy and the detection of disease recurrence or metastasis.

3\. Prior treatment with anti-EGFR monoclonal antibodies, EGFR tyrosine kinase inhibitors, or other EGFR-targeted therapies (e.g., cetuximab, nimotuzumab, panitumumab).

4\. Known hypersensitivity or anaphylactic reaction to any component of the study treatment.

5\. History of organ transplantation or autologous/allogeneic stem cell transplantation.

6\. History of other malignancies other than CRC within the past 5 years, except cured carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin.

7\. Other concomitant antitumor therapy.

8\. Symptomatic brain and/or leptomeningeal metastases.

9\. Participation in any investigational drug treatment or use of an investigational device within 4 weeks before first dose.

10\. Currently receiving chronic systemic immunotherapy or hormonal therapy other than physiologic replacement therapy.

11\. Any unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, angina that began within the last 3 months, congestive heart failure (New York Heart Association \[NYHA\] class ≥ II), myocardial infarction within 6 months before enrollment, severe arrhythmia requiring medical treatment, or hepatic, renal, or metabolic disease.

12\. Acute or subacute intestinal obstruction, or a history of inflammatory bowel disease.

13\. Participants with severe bone marrow failure.

14\. Any disease, metabolic disorder, or physical examination or laboratory finding that suggests a contraindication to the study drug or a high risk of treatment complications.

15\. Known or self-reported human immunodeficiency virus (HIV) infection.

16\. HBV-DNA positive (viral load \>10\^3 copies/mL).

17\. Pregnancy or lactation.

18\. Prior treatment with any therapy targeting tumor immune mechanisms, including immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., antibodies targeting ICOS, CD40, CD137, GITR, or OX40), or immune cell therapy.

19\. Received a live vaccine within 4 weeks before first dose, or plans to receive a live vaccine during the study.

20\. Any condition that, in the investigator's opinion, may make it risky to receive the study drug, or may interfere with the evaluation of the study drug, participant safety, or interpretation of study results.

What this study is about