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;
1. Mixed carcinoma with non-neuroendocrine tumor components;
2. Active brain metastases (patients with stable disease for 3 months after treatment without the need for continued glucocorticoid therapy are eligible for enrollment); known leptomeningeal metastases; isolated central nervous system (CNS) disease progression without evidence of progression outside the CNS;
3. A history of hypersensitivity to interleukin-2 (IL-2), fludarabine, cyclophosphamide, tocilizumab, or any component of the infusion product formulation; or patients with a history of specific allergic disorders (asthma, rubella, eczematous dermatitis);
5. Any systemic antineoplastic therapy within 4 weeks or 5 half-lives prior to the first administration of NEUK203-13 Injection, whichever is shorter;
Sequential
Biological/Vaccine: NK Cell Therapy Product Derived from Induced Pluripotent Stem Cells (iPSCs) Engineered with Anti-DLL3 CAR Construct, Followed by Differentiation and Expansion
Biological/VaccineIntravenous infusion of NEUKIO203-13 d1,d4,d7 and IL-2 6 mIU d1,d4,d7 and d10 was administered following lymphodepletion with cyclophosphamide combined with fludarabine.
The incidence and severity of Adverse Events (AEs) / Serious Adverse Events (SAEs) / Adverse Events of Special Interest (AESIs).
This endpoint aims to systematically monitor, record, and evaluate the safety profile of the study treatment by assessing the incidence, severity, duration, and causal relationship of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) throughout the study period.
Detect the number of NEUK203-13 cells in peripheral blood and calculate the PK parameters.
Quantification of NEUK203-13 Cells in Peripheral Blood and Pharmacokinetic (PK) Parameter Calculation
Ratio of DLL3 expression in tumor tissues versus response rate
Correlation Analysis Between DLL3 Expression Ratio in Tumor Tissues and Clinical Response Rate
Objective Response Rate (ORR)
The proportion of evaluable patients who achieve a complete response (CR) or partial response (PR) confirmed by two consecutive assessments separated by a minimum 4-week interval. CR is defined as the disappearance of all target and non-target lesions with no new lesions detected; PR refers to a ≥30% reduction in the sum of the longest diameters of target lesions, with no progression of non-target lesions or new lesions. ORR will be calculated as the percentage of patients with CR or PR relative to the total evaluable study cohort.
Duration of Response (DoR)
The time interval from the first documentation of CR or PR (per the above criteria) to the first confirmed occurrence of disease progression (per RECIST v1.1) or death from any cause, whichever occurs first. For patients who maintain a response until the end of the study, DoR will be censored at the date of the last tumor assessment.
Detect the cytokines associated with the tumor cell killing process (IFN-γ, TNF-α) in peripheral blood.
The absolute concentration of IFN-γ and TNF-α in peripheral blood at each time point; The dynamic changes in cytokine levels relative to baseline values (calculated as percentage change or fold change); The correlation between cytokine level fluctuations and clinical endpoints (e.g., objective response rate, disease control rate) or biomarker changes (e.g., tumor cell burden, immune cell subsets).
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Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Lead sponsor
Neukio Biotherapeutics (Shanghai) Co., Ltd.
Collaborator
