A Clinical Study of Lutetium[177Lu] Oxodotreotide Injection in Patients With Advanced Neuroendocrine Neoplasms

Inclusion

• Positive human immunodeficiency virus (HIV) antibody.
• Enrolled in other clinical trials and received investigational drugs within 4 weeks prior to the first dose.
• Received palliative radiotherapy for bone metastases within 2 weeks prior to the first dose.
• Serum albumin \< 30 g/L.
• Received local anti-tumor treatments such as surgery (excluding biopsy), radical radiotherapy, hepatic arterial chemoembolization, cryoablation or radiofrequency ablation for liver metastases within 4 weeks before the first dose.
• Any uncontrolled diseases, mental disorders or surgical conditions that may affect study completion (including poor treatment compliance) or make subjects ineligible for the investigational product.
• History of other confirmed malignant tumors (excluding those with complete treatment and expected no recurrence within 5 years).
• Contraindications to contrast-enhanced CT and MRI contrast agents due to allergic reactions or renal insufficiency.
• Hemoglobin \< 100 g/L, white blood cell count \< 2.0×10⁹/L, or platelet count \< 100×10⁹/L.
• Have at least one measurable lesion at baseline per RECIST 1.1 criteria. 7. All baseline target lesions (per RECIST 1.1) must be confirmed as somatostatin receptor-positive via ⁶⁸Ga-Dotatate PET/CT.Notes:
• Uncontrolled congestive heart failure, including baseline left ventricular ejection fraction (LVEF) \< 50%.
• Received systemic anti-tumor therapies including targeted therapy, immunotherapy, anti-tumor traditional Chinese medicine therapy or chemotherapy within 4 weeks before the first study drug administration.
• International Normalized Ratio (INR) \> 1.5 or activated partial thromboplastin time (APTT) \> 1.5×ULN.
• ⁶⁸Ga-Dotatate PET/CT images obtained within 24 weeks before the first drug administration are acceptable if investigators verify they can reflect the somatostatin receptor status at enrollment;
• Uncontrolled diabetes mellitus, including baseline fasting blood glucose \> 2×ULN.
• Histologically confirmed, unresectable locally advanced or metastatic neuroendocrine neoplasms (NENs) \[excluding well-differentiated (G1 and G2) gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and neuroendocrine carcinomas (NECs)\]. The target population mainly includes:(1)Grade 3 (G3) GEP-NET with Ki-67 index ≤ 55% (2)Other non-gastroenteropancreatic originated NEN, including pulmonary/thymic NEN, primary NEN of other sites, and NEN of unknown primary origin (3)Pheochromocytoma and paraganglioma (PPGL) Note: Histopathological specimens collected within 3 years prior to the first study drug administration are acceptable, provided that investigators confirm they can represent the pathological status at enrollment; otherwise, fresh specimens shall be collected.4\. Patients who have failed prior optimal available treatment, are intolerant to optimal available treatment, or have no access to optimal available treatment, with no restriction on the number of prior treatment lines.Note: Optimal available treatment is determined by investigators based on individual subject conditions, including chemotherapy, targeted therapy, biologic therapy, etc.
• Prior history of peptide receptor radionuclide therapy (PRRT).
• Confirmed brain metastases (excluding those stabilized for at least 24 weeks before the first administration).
• Subjects receiving short-acting octreotide who cannot discontinue it within 24 hours before and after administration of Lutetium-177 Oxotreotide Injection; or subjects receiving octreotide acetate microspheres who cannot stop the treatment within 6 weeks prior to the first dose of Lutetium-177 Oxotreotide Injection. Note: Further evaluation is required for subjects receiving other somatostatin analog (SSA) treatments.
• Based on the patient's disease characteristics, the investigator judges that alternative treatments such as chemotherapy and targeted therapy are more suitable for the patient than the study treatment, meaning the investigational product is not the optimal clinical treatment option.
• Total serum bilirubin \> 3 times the upper limit of normal (ULN).
• Toxicities from previous anti-tumor therapies have not recovered to Grade 1 or lower (alopecia excluded).
• Positive hepatitis B surface antigen (HBsAg) combined with positive HBV-DNA (≥1×10⁴ copies/mL or confirmed positive per local study center criteria); or positive hepatitis C virus (HCV) antibody combined with positive HCV-RNA (≥1×10³ copies/mL).
• Known hypersensitivity to any ingredients or excipients of Lutetium-177 Oxotreotide Injection and octreotide acetate microspheres.
• Serum creatinine \> 150 μmol/L (1.7 mg/dL) or creatinine clearance rate \< 50 mL/min (calculated by Cockcroft-Gault formula).
• Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2.5×ULN.
• Pregnant or breastfeeding females.
• Have documented disease progression within 1 year prior to the first study drug administration, and have not received any other systemic anti-tumor therapy after disease progression.
• Somatostatin receptor positivity is defined as lesion uptake higher than normal liver uptake;
• Presence of active infections requiring intravenous antibacterial drugs or inpatient intervention.
• Subjects with any target lesion confirmed somatostatin receptor-negative by ⁶⁸Ga-Dotatate PET/CT shall be excluded.8\. Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at baseline.9\. Subjects of childbearing potential must voluntarily use effective contraceptive methods throughout the treatment period and for 4 months (male) or 7 months (female) after the last dose of investigational product, such as condoms, oral/injectable contraceptives, intrauterine devices, etc.Exclusion Criteria

Exclusion

Exclusion criteria not yet provided.