A Study to Explore the Safety, Tolerability, and Preliminary Efficacy of NEUK203-13 Injection in Patients With Neuroendocrine Tumors Who Have Failed Systemic Therapy
This is a Phase I clinical trial being conducted in humans for the first time, aiming to evaluate a novel cell therapy called NEUK203-13 Injection for the treatment of patients with advanced small cell lung cancer (SCLC) who have failed systematic therapy or late stage neuroendocrine tumors(NETs). The primary goal of the study is to determine the safety and tolerability of this new therapy and to preliminarily observe its anti-tumor effects. NEUK203-13 Injection is an off-the-shelf CAR-NK cell therapy developed based on induced pluripotent stem cell (iPSC) technology, targeting the DLL3 protein highly expressed in SCLC or other neuroendocrine tumors(NETs) . Primary Objective Primary Endpoint aims to evaluate safety and tolerability Secondary Endpoints aim to preliminarily observe efficacy and investigate the pharmacokinetics of the drug in the body. Two pre-set dose levels are planned, with an enrollment of 7-9 patients. Treatment Regimen 1. Lymphodepletion Conditioning: Chemotherapy (Cyclophosphamide + Fludarabine) before cell infusion to clear lymphocytes in the body. 2. Cell Infusion: NEUK203-13 is administered via intravenous infusion, d1，d4 and d7 for three doses. 3. Supportive Medication: Concurrent use of IL-2 (Interleukin-2) d1, d4, d7 and d10 to support NK cell persistence. Target Patient Population Patients with advanced SCLC who have progressed after prior platinum-based chemotherapy or late stage neuroendocrine tumors(NETs) and have a relatively good performance status. Key Monitoring Focus Close monitoring of risks specific to cell therapy, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). In short, this study represents the first clinical exploration of NEUK203-13 Injection in patients with advanced small cell lung cancer or other neuroendocrine tumors(NETs). Its primary focus is on safety, while simultaneously gathering preliminary signals on whether the therapy can control tumors, thereby laying the foundation for subsequent clinical development.
• 1\. Understand and voluntarily sign the Informed Consent Form (ICF);
• 2\. Aged ≥ 18 years and \< 75 years at the time of signing the ICF, regardless of gender;
• 3\. Pathologically confirmed neuroendocrine tumors, including small cell lung cancer (SCLC), etc.;
• 4\. Previous failure or intolerance to systemic therapy, or recurrence after remission: among them, patients with small cell lung cancer must have received at least platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors in previous treatments, with imaging evidence of disease progression after treatment;
• 5\. Must provide tissue samples for biomarker analysis, preferably newly obtained tissues. For patients unable to provide newly obtained tissues, 4 unstained sections of archived formalin-fixed, paraffin-embedded (FFPE) tissues can be provided (at least 1 patient with high DLL3 expression shall be enrolled in each dose group: high expression is defined as positive staining in ≥ 50% of tumor cells; preference is given to enrolling DLL3-positive patients);
• 6\. Have at least one measurable lesion as the target lesion (per RECIST v1.1 criteria);
• 7\. Expected survival ≥ 3 months;
• 8\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• 9\. Have adequate bone marrow reserve and organ function within 7 days before the first administration of NEUK203-13 Injection:
• 10\. Sufficient bone marrow function (no supportive therapy within 14 days before the first administration): hemoglobin (Hb) ≥ 90 g/L, platelets (PLT) ≥ 75 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• 11\. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), total bilirubin (TBIL) \< 1.5 × ULN;
• 12\. Renal function: serum creatinine (Scr) ≤ 1.5 × ULN and creatinine clearance rate (Ccr) ≥ 60 mL/min (calculated according to the Cockcroft-Gault formula); Coagulation function: prothrombin time (PT) ≤ 1.5 × ULN, international normalized ratio (INR) ≤ 2.0;
• 13\. Female patients of childbearing potential or male patients whose partners are of childbearing potential agree to use highly effective contraceptive measures from any dose administration in the study until 6 months after the last dose of the study.