A Study of NBL-028 in Patients With Advanced Solid Tumors

Inclusion criteria

• Patients ≥18 years old, should have fully understood the study and voluntarily signed an informed consent form.
• Patients with pathologically diagnosed advanced solid tumors with positive expression of CLDN6. Stage I: Patients have failed or cannot tolerate standard of care, or without standard treatment; Stage Ⅱ: Previously treated advanced solid tumors.
• Be able to provide previously well-preserved tumor tissue sections, or agree to undergo tumor tissue biopsy for central laboratory biomarker testing.
• At least one measurable target lesion according to RECIST 1.1.
• ECOG performance status of 0 or 1 at screening.
• Life expectancy ≥3 months.
• Adequate organ function within 7 days prior to the first dose defined as: Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥100×10^9/L;. Hemoglobin (HGB) ≥90 g/L; Serum creatinine ≤ 1.5 × ULN or Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥50 mL/min; Total bilirubin (TBIL) ≤1.5×ULN (≤3×ULN when patients with Gilbert's disease); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (≤5×ULN if liver involvement is known).
• Serum pregnancy test for women of childbearing potential (WOCBP) is negative within 7 days prior to the first dose of the investigational drug. The patient and his/her spouse must agree to use adequate contraception from signing of informed consent form (ICF) to 3 months after the last dose, during which women should be non-lactating and men should refrain from donating sperm.

Exclusion criteria

• Previously received CLDN6-targeted or CD137-targeted treatment.
• Known uncontrolled central nervous system (CNS) cancer including CNS metastasis, meningeal metastasis, or spinal cord compression.
• Patients with high risk of bleeding due to tumor invasion of important arteries.
• Has uncontrolled serous cavity effusion (such as pleural effusion, abdominal effusion, or pericardial effusion, etc) requiring repeated drainage.
• Has adverse events due to previous anti-tumor treatments that have not yet recovered to ≤Grade 1 according to NCI-CTCAE v5.0;
• Developed immune-related adverse events (irAE) of grade ≥3 (CTCAE 5.0) with prior immunotherapy
• Known to exist any other malignant tumor requiring intervention.
• Have received anti-tumor treatments (such as chemotherapy, targeted therapy, biological therapy, etc.) or any other investigational drugs or treatments within 4 weeks or 5 half-lives, whichever is shorter.
• Have received a live viral vaccine within 4 weeks before the first dose of study drug.
• Have received immunosuppressive medications within 2 weeks prior to the first dose of study drug.
• Have active or serious bacterial, fungal, or viral infection requiring systemic anti-infective treatment within 2 weeks prior to the first dose of study drug.
• Have received radiation therapy or other localized palliative treatment within 2 weeks before the first dose of study drug.
• Have undergone major surgery within 4 weeks before the first dose of study drug, or scheduled to have major surgery during the study.
• Have a history of serious cardiovascular disease.
• Have active or history of autoimmune diseases.
• A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
• Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis.
• Hypersensitive to humanized monoclonal antibody products.
• Women during lactation or pregnancy.
• Any male and female patients with fertility who refuse to use effective contraceptive methods throughout the entire trial period and within six months after the last administration.
• Other conditions that, in the opinion of the investigator, may affect the safety or compliance of drug treatment in this study, including but not limited to: psychiatric disorders, any severe or uncontrollable diseases, etc.