A Clinical Trial on the Efficacy and Safety of TQB6411 for Injection

Korábbi kezelés

• History of or concurrent other malignancies, except for: other malignancies treated with surgery alone and achieving ≥5 years of disease-free survival (DFS); or cured carcinoma in situ of cervix, non-melanoma skin cancer, or superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading basement membrane)].
• Major surgery (Grade 3 or above per National Surgical Classification Catalog 2022), significant traumatic injury within 4 weeks prior to first dose, planned major surgery during study (except protocol-specified procedures), or presence of unhealed wounds/fractures.
• Any bleeding or hemorrhagic events ≥CTCAE grade 3 within 4 weeks prior to first dose.
• Arterial/venous thromboembolic events within 6 months prior to first dose, including: cerebrovascular accidents (including transient ischemic attack (TIA), excluding lacunar infarction), deep vein thrombosis, or pulmonary embolism (implantable venous port- or catheter-related thrombosis or superficial venous thrombosis not considered "severe" thromboembolism).
• Prior or planned allogeneic bone marrow or solid organ transplantation.
• Uncontrolled autoimmune diseases requiring immunosuppressants or systemic corticosteroids (>10mg prednisone/day equivalent) within 7 days prior to first dose.
• Tumor-related conditions and treatments:
  • Chemotherapy, immunotherapy, or small-molecule targeted therapy within 3 weeks prior to first dose or within 5 half-lives (whichever shorter); prior local radiotherapy allowed if: completed >4 weeks (>2 weeks for brain) before study treatment, and target lesions are outside radiation field or show progression within field;
  • National Medical Products Administration (NMPA)-approved traditional Chinese medicines with antitumor indications within 1 week prior to first dose;
  • Tumor invading major vessels or judged likely to cause fatal hemorrhage;
  • Uncontrolled effusions/ascites requiring recurrent drainage;
  • Spinal cord compression, leptomeningeal metastases, or brain metastases with symptoms controlled <4 weeks, or requiring steroids/dehydrating agents within 2 weeks before treatment.
• Participation in other antitumor clinical trials within 4 weeks prior to first dose.

Más betegség

• Diseases affecting intravenous injection or blood sampling.
• Active tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced/radiation pneumonitis requiring treatment, clinically significant active pneumonia, history of interstitial lung disease (ILD) requiring treatment, or current ILD.
• History of psychotropic drug abuse or mental disorders.
• History of hepatic encephalopathy.
• Active or uncontrolled severe infection (≥CTCAE grade 2).
• Renal failure requiring hemodialysis or peritoneal dialysis.
• Immunodeficiency including HIV positivity or other acquired/congenital immunodeficiency diseases.
• Epilepsy requiring treatment.
• Known hypersensitivity to study drug or excipients.
• Other conditions judged by investigator to jeopardize participant safety or study completion.

Laborértékek

• Adverse reactions from prior therapies not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v6.0 grade ≤1, except for: grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non-clinically significant asymptomatic grade 2 laboratory abnormalities, hypothyroidism stabilized with hormone replacement, or other toxicities judged by investigator as non-safety risks.
• Active viral hepatitis with poor control, except: hepatitis B surface antigen (HBsAg)-positive participants with HepatitisBvirus Deoxyribonucleic acid (HBV DNA) <500 IU/mL (2500 copies/mL) who agree to receive anti-HBV therapy throughout study; or hepatitis C virus (HCV)-infected participants (Hepatitis C Virus Antibody or Ribonucleic Acid positive) with hepatitis C virus Ribonucleic Acid (HCV RNA) ≤ULN continuing approved antiviral therapy.
• Significant cardiovascular diseases including:
  • Cardiac dysfunction ≥New York Heart Association (NYHA) class II or Left Ventricular Ejection Fractions (LVEF) <50% by echocardiography;
  • Clinically significant ventricular arrhythmia history (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or arrhythmias requiring continuous antiarrhythmic therapy (participants with stable atrial fibrillation controlled solely by β-blockers may be included after investigator assessment);
  • Unstable angina;
  • Myocardial infarction within 12 months;
  • Cardio contraction time (QTc) >450ms (male) or >470ms (female) (if abnormal, measure three times at ≥2-minute intervals and average; corrected by Fridericia or Bazett method);
  • Congenital long QT syndrome or family history.
• Poorly controlled diabetes (fasting blood glucose >10mmol/L).
• Prior treatment with: Epidermal Growth Factor Receptor/cellular-mesenchymal epithelial transition factor (EGFR/c-Met)-targeted antibody-drug conjugates (ADCs); or topoisomerase I inhibitors (Non-Small Cell Lung Cancer only) or topoisomerase I inhibitor-based ADCs.
• Prior EGFR/c-Met-targeted Monoclonal Antibody (mAbs)/bispecifics with: ≥grade 4 toxicity, permanent discontinuation due to toxicity, ≥grade 3 infusion reactions, or ≥grade 3 myalgia.

Egyéb

• Active syphilis requiring treatment.

• Participants voluntarily participate in this study, sign the informed consent form, and demonstrate good compliance;
• Age between 18 and 75 years (calculated based on the date of signing the informed consent form);
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Expected survival greater than 12 weeks;
• At least one measurable lesion according to RECIST v1.1 criteria;
• Laboratory test results meeting the following criteria (no blood transfusion within 14 days or hematopoietic growth factor administration within 7 days prior to screening):
  • Hemoglobin (HGB) ≥ 90 g/L;
  • Absolute neutrophil count (NEUT) ≥ 1.5×10⁹/L;
  • Platelet count (PLT) ≥ 90×10⁹/L;
  • Total bilirubin (TBIL) ≤ 1.5×Upper Limit of Normal (ULN);
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (≤ 5×ULN if liver metastases are present);
  • Serum creatinine (CR) ≤ 1.3×ULN or creatinine clearance rate (CCR) ≥ 50 mL/min;
  • Prothrombin time (PT), activated partial thromboplastin time (APTT), and international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy within the past 2 weeks);
• Lung cancer confirmed by histology or cytology；
• Willing to provide qualified tumor tissue samples for immunohistochemical and amplification testing, unless the participant has no eligible archived specimens and is unsuitable or refuses re-biopsy;
• Women of childbearing potential must agree to use effective contraception during the study and for 6 months after study completion, with a negative serum or urine pregnancy test within 7 days before enrollment; male participants must agree to use effective contraception during the study and for 6 months after study completion (see Section 5.5 for details).