A Multicenter, Prospective, Non-Interventional Real-World Study of Iparomlimab and Tuvonralimab Injection (QL1706) in the Treatment of Locally Advanced or Metastatic Solid Tumors

Inclusion criteria

• 1) Histologically or cytologically confirmed locally advanced or metastatic solid tumors with disease progression (radiographic or clinical) after ≥1 line of prior standard therapy, unsuitable for/intolerant to standard therapy. Includes but not limited to: Gastrointestinal tumors (colorectal cancer, hepatocellular carcinoma, esophageal cancer, biliary tract cancer, pancreatic cancer, gastric cancer), Breast cancer, Non-small cell lung cancer (NSCLC), Small cell lung cancer (SCLC), Soft tissue sarcoma;
• 2) ECOG performance status 0-2;
• 3) ≥1 measurable lesion per RECIST v1.1 ;
• 4) Adequate organ function meeting ALL criteria below:

• Hematology (without transfusion/G-CSF support within 7 days):

Absolute neutrophil count (ANC) ≥1.5×10⁹/L Platelets ≥100×10⁹/L Hemoglobin ≥90 g/L

• Biochemistry :

Total bilirubin (TBIL) ≤2×ULN ALT/AST ≤2.5×ULN (≤5×ULN if liver metastases present) Serum creatinine (Cr) ≤1.5×ULN Albumin ≥28 g/L

• Urinalysis :

Urine protein <2+ (dipstick) If protein ≥2+, 24h urinary protein ≤1.0 g

• Coagulation (without anticoagulants):

PT/APTT/INR ≤1.5×ULN

• 5) Life expectancy ≥12 weeks;
• 6) Contraception : Females of childbearing potential or males with partners of childbearing potential must use effective contraception during treatment and for 6 months post-treatment;
• 7) Signed informed consent and protocol compliance.

Exclusion criteria

• 1) Tumor-Related Conditions

• Known CNS metastases (except those radiologically stable ≥4 weeks after radiotherapy);
• Other malignancies within past 5 years, excluding:

Cured basal/squamous cell skin cancer Localized low-risk prostate cancer Cervical/breast carcinoma in situ

• Severe bone lesions from metastatic disease, including:

Uncontrolled bone pain Pathologic fractures at critical sites (within 6 months) or impending spinal cord compression;

• Uncontrolled effusions requiring recurrent drainage (pleural/pericardial/ascites), per investigator assessment.
• 2) Prior Anti-tumor Therapy

• Prior systemic therapy with CTLA-4 inhibitors or other ICIs;
• Any anti-tumor treatment within 4 weeks before first dose, including:

Surgery/chemotherapy/palliative radiotherapy to non-target lesions/hormonal/targeted/biologic/immunotherapy;

• Treatment-related toxicities not recovered to CTCAE grade ≤1 (exceptions: alopecia/platinum-induced neuropathy ≤ grade 2).
• 3) Comorbidities & History

• Arterial thromboembolism within 6 months (MI/unstable angina/stroke/TIA);
• Symptomatic heart failure (NYHA class III-IV), unstable angina, or uncontrolled arrhythmia;
• Severe pulmonary disease : ILD/COPD/symptomatic bronchospasm;
• Active uncontrolled infection (≥CTCAE grade 2), including:

HIV Active HBV (DNA ≥500 IU/mL) HCV (Ab+ with detectable RNA) HBV/HCV co-infection;

• History of neurologic/psychiatric disorders;
• Recent or current substance abuse;
• Prior allogeneic organ/hematopoietic stem cell transplantation.
• 4) Hypersensitivity to study drug or its excipients.
• 5) Active autoimmune disease requiring treatment or history within 2 years. Exceptions: Vitiligo/alopecia/psoriasis not needing systemic therapy Hypothyroidism managed only with hormone replacement Type 1 diabetes controlled solely with insulin.
• 6) Pregnant/lactating women;
• 7) Any uncontrolled systemic disease increasing study risk (per investigator);
• 8) Other unsuitable conditions determined by investigator.