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

Korábbi kezelés

• 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.
• 7. Other concomitant antitumor therapy.
• 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.
• 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.

Más betegség

• 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.
• 12. Acute or subacute intestinal obstruction, or a history of inflammatory bowel disease.
• 13. Participants with severe bone marrow failure.
• 15. Known or self-reported human immunodeficiency virus (HIV) infection.
• 16. HBV-DNA positive (viral load >10\^3 copies/mL).
• 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.

Laborértékek

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

Egyéb

• 8. Symptomatic brain and/or leptomeningeal metastases.
• 17. Pregnancy or lactation.

• 1. Participants voluntarily agree to participate in this study, sign the informed consent form, and strictly comply with the study protocol requirements.
• 2. Age ≥18 years and ≤75 years at enrollment, male or female.
• 3. Histopathologically confirmed recurrent or metastatic colorectal adenocarcinoma; the enrolled population must have low-level microsatellite instability (MSI-L) or microsatellite stable (MSS)/mismatch repair-proficient (pMMR) tumors and be RAS and BRAF wild-type.
• 4. At least one measurable tumor lesion per RECIST v1.1.
• 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 6. Expected survival ≥3 months.
• 7. Recovered from toxicities related to prior therapy before study enrollment.
• 8. Adequate vital organ function as follows: Hematology: absolute neutrophil count (ANC) ≥1.5 × 10\^9/L, platelet count (PLT) ≥90 × 10\^9/L, hemoglobin (Hb) ≥90 g/L. Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN); for participants with liver metastases, AST and ALT ≤5 × ULN; serum total bilirubin (TBIL) ≤1.5 × ULN (for participants with Gilbert's syndrome, TBIL <3 × ULN); albumin (ALB) ≥30 g/L. Thyroid function: thyroid-stimulating hormone (TSH) ≤1 × ULN (if abnormal, free triiodothyronine [FT3] and free thyroxine [FT4] levels should also be assessed; participants with normal FT3 and FT4 may be enrolled). Coagulation function: activated partial thromboplastin time (APTT) ≤1.5 × ULN, international normalized ratio (INR) ≤1.5, prothrombin time (PT) ≤1.5 × ULN. Urine protein: qualitative urine protein ≤1+ (if ≥2+, a 24-hour urine protein test is required; if the result is <1 g, enrollment is permitted). Cardiac left ventricular ejection fraction (LVEF) ≥50%.
• 9. Participants of childbearing potential must use adequate contraception during the study and for 120 days after study completion; female participants must have a negative serum pregnancy test within 7 days before study enrollment and must not be breastfeeding.