Ignite Creation Date:
2026-03-26 @ 3:18 PM
Ignite Modification Date:
2026-03-30 @ 4:21 AM
Study NCT ID:
NCT07366658
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-01-26
First Post:
2026-01-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety, Tolerability and Preliminary Efficacy of NEUK203-13 in Refractory Neuroendocrine Tumor Patients
Sponsor:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Organization:
Study Overview
Official Title:
A Study to Explore the Safety, Tolerability, and Preliminary Efficacy of NEUK203-13 Injection in Patients With Neuroendocrine Tumors Who Have Failed Systemic Therapy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NEUK203-13
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. 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.
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.
Detailed Description:
NEUK203-13 Injection is a chimeric antigen receptor (CAR)-natural killer (NK) cell therapy (CAR-NK) derived from induced pluripotent stem cells (iPSCs). Through site-specific gene editing, it expresses a CAR structure targeting Delta-like Protein 3 (DLL3). Specifically, the CAR construct is introduced into NK cells via transgenic engineering, enabling precise recognition and elimination of malignant/cancer cells expressing the specific antigen DLL3. Beyond CAR molecular transgenesis, an IL-15RF fusion gene is inserted at the CD38 locus to enhance the pharmacokinetic (PK) properties of CAR-iNK cells. Additionally, the immune checkpoint receptor TIM3 is knocked out to improve resistance to the immunosuppressive tumor microenvironment, and a variant CD16 (vCD16, a cleavage-resistant CD16) is inserted to augment antibody-dependent cellular cytotoxicity (ADCC) when used in combination with therapeutic antibodies.
Using clinical-scale production batches and processes, in vitro pharmacodynamic studies and evaluations of NEUK203-13 Injection were conducted across multiple dimensions, including:
1. Nonspecific cytotoxicity against target cells (human chronic myelogenous leukemia cell line K562) at different process stages and in fresh bulk cells;
2. Specific cytotoxicity against tumor cells (small cell lung cancer cell lines SHP-77 and H82 with high DLL3 expression, and the human B-lymphoblastic leukemia cell line NALM6-DLL3 with stable exogenous DLL3 expression as target cells);
3. Cell viability post cryopreservation and thawing;
4. Cytotoxic activity (both nonspecific and specific) post cryopreservation and thawing.
NEUK203-13 represents an iterative upgrade of the first-generation product NEUK200-13. The accelerated advancement of NEUK203-13 into clinical research is based on the established clinical safety data of NEUK200-13 and the superior preclinical data of NEUK203-13.
Using clinical-scale production batches and processes, in vitro pharmacodynamic studies and evaluations of NEUK203-13 Injection were conducted across multiple dimensions, including:
1. Nonspecific cytotoxicity against target cells (human chronic myelogenous leukemia cell line K562) at different process stages and in fresh bulk cells;
2. Specific cytotoxicity against tumor cells (small cell lung cancer cell lines SHP-77 and H82 with high DLL3 expression, and the human B-lymphoblastic leukemia cell line NALM6-DLL3 with stable exogenous DLL3 expression as target cells);
3. Cell viability post cryopreservation and thawing;
4. Cytotoxic activity (both nonspecific and specific) post cryopreservation and thawing.
NEUK203-13 represents an iterative upgrade of the first-generation product NEUK200-13. The accelerated advancement of NEUK203-13 into clinical research is based on the established clinical safety data of NEUK200-13 and the superior preclinical data of NEUK203-13.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: