Safety, Tolerability and Preliminary Efficacy of NEUK203-13 in Refractory Neuroendocrine Tumor Patients

NCT07366658 | Not Yet Recruiting Phase 1

• 1 other identifier: NEUK203-13-IIT-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Lymphodepletion Conditioning: Chemotherapy (Cyclophosphamide + Fludarabine) before cell infusion to clear lymphocytes in the body.
2. 2.Cell Infusion: NEUK203-13 is administered via intravenous infusion, d1，d4 and d7 for three doses.
3. 3.Supportive Medication: Concurrent use of IL-2 (Interleukin-2) d1, d4, d7 and d10 to support NK cell persistence.

Conditions

SCLC, Extensive Stage; Neuroendocrine Tumors

Keywords

Car-NK cells; iPSC

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (5)

• Detect the number of NEUK203-13 cells in peripheral blood and calculate the PK parameters.

  12 months

• Ratio of DLL3 expression in tumor tissues versus response rate

  12 months

• Objective Response Rate (ORR)

  12 months

• Duration of Response (DoR)

  12 months

• Disease Control Rate (DCR)

  12 months

Other Outcomes (1)

• Detect the cytokines associated with the tumor cell killing process (IFN-γ, TNF-α) in peripheral blood.

  12 months

Study Arms (1)

Intravenous infusion of NEUKIO203-13 was administered following lymphodepletion

EXPERIMENTAL

Intravenous infusion of NEUKIO203-13 was administered following lymphodepletion with cyclophosphamide combined with fludarabine.

Biological: Biological/Vaccine: NK Cell Therapy Product Derived from Induced Pluripotent Stem Cells (iPSCs) Engineered with Anti-DLL3 CAR Construct, Followed by Differentiation and Expansion

Interventions

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

Intravenous 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.

Intravenous infusion of NEUKIO203-13 was administered following lymphodepletion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Understand and voluntarily sign the Informed Consent Form (ICF);
• \. Aged ≥ 18 years and \< 75 years at the time of signing the ICF, regardless of gender;
• \. Pathologically confirmed neuroendocrine tumors, including small cell lung cancer (SCLC), etc.;
• \. 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;
• \. 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);
• \. Have at least one measurable lesion as the target lesion (per RECIST v1.1 criteria);
• \. Expected survival ≥ 3 months;
• \. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• \. Have adequate bone marrow reserve and organ function within 7 days before the first administration of NEUK203-13 Injection:
• \. 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;
• \. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN), total bilirubin (TBIL) \< 1.5 × ULN;
• \. 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;
• \. 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.

You may not qualify if:

• \. Mixed carcinoma with non-neuroendocrine tumor components;
• \. 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;
• \. 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);
• \. Prior receipt of any of the following treatments:
• \. Any systemic antineoplastic therapy within 4 weeks or 5 half-lives prior to the first administration of NEUK203-13 Injection, whichever is shorter;
• \. Radiotherapy not involving the thoracic cavity within 2 weeks prior to the first administration of NEUK203-13 Injection, or radiotherapy involving the thoracic cavity within 4 weeks prior to the first administration of the study drug, whichever is longer;
• \. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study;
• \. Prior vaccination with an antineoplastic vaccine, or receipt of a live vaccine within 4 weeks prior to the first administration of NEUK203-13 Injection;
• \. Major surgery or severe trauma within 4 weeks prior to the first administration of NEUK203-13 Injection;
• \. Active autoimmune disease or a history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); exceptions include patients with vitiligo, patients with a history of childhood asthma/allergies that have resolved completely and require no intervention in adulthood, patients with autoimmune-mediated hypothyroidism receiving a stable dose of thyroid replacement hormone, and patients with type 1 diabetes receiving a stable dose of insulin;
• \. A history of immunodeficiency, including positive HIV test results, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation;
• \. Severe infection (CTCAE \> Grade 2) within 4 weeks prior to the first administration of NEUK203-13 Injection, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc.; baseline chest imaging indicating active pulmonary inflammation; or presence of signs and symptoms of infection requiring oral or intravenous antibiotic therapy within 2 weeks prior to the first administration of the study drug (except for prophylactic antibiotic use);
• \. Tuberculosis infection identified by medical history or CT examination; Active hepatitis B (HBV DNA ≥ 500 IU/mL), hepatitis C (positive anti-HCV antibodies and HCV-RNA above the lower limit of detection of the assay), or positive syphilis test results (including positive RPR or TPPA);
• \. Prior diagnosis of any other malignant tumor, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or adequately treated localized prostate cancer;
• \. Pregnant or lactating women;

Sponsors & Collaborators

• Neukio Biotherapeutics (Shanghai) Co., Ltd.: collaborator
• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital of CICAMS

Beijing, China

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Biological Products; Engineering

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Complex Mixtures; Technology, Industry, and Agriculture

Study Officials

• Shuhang Wang, PhD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Ning Li, MD

CONTACT

86-010-87788713; lining@cicams.ac.cn

Shuhang Wang, PhD

CONTACT

13581809307; wangshuhang@cicams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two dose groups are preset. For the first subject in the initial dose group, NEUK203-13 Injection is administered intravenously at a dose of 2×10⁹ cells, once every 3 days (Q3D) for a total of 3 consecutive doses. The Safety Monitoring Committee (SMC) may decide to proceed to the second dose group based on the available safety/tolerability data and pharmacokinetic/biomarker data. For subjects in the second dose group, NEUK203-13 Injection is administered intravenously at a dose of 4×10⁹ cells, once every 3 days (Q3D) for a total of 3 consecutive doses.

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 26, 2026
• Study Start: February 20, 2026
• Primary Completion (Estimated): October 20, 2026
• Study Completion (Estimated): January 20, 2027
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)