Acute Myeloid Leukemia (AML), Breast Cancer, Cancer, Colorectal Cancer (Locally Advanced or Metastatic), Glioblastoma, Liver Cancer, Melanoma (Skin Cancer), Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma, Non Hodgkin Lymphoma, Non-Small Cell Lung Cancer (NSCLC), Ovarian Cancer, Pancreatic Ductal Adenocarcinoma (PDAC), Prostate Cancer - Recurrent
Conditions
Keywords
CAR-NK, Solid tumor, Dual-target CAR, ctDNA, CAR-T, Breast cancer, Non-small cell lung cancer (NSCLC), Colorectal cancer (CRC), Prostate cancer, Pancreatic ductal adenocarcinoma (PDAC), Ovarian, fallopian tube, and primary peritoneal cancers, Glioblastoma and other high-grade gliomas, Melanoma, Acute myeloid leukemia (AML), Non-Hodgkin lymphoma (NHL), especially DLBCL and follicular lymphoma, Multiple myeloma (especially relapsed/refractory), Liver cancer (hepatocellular carcinoma, HCC)
Brief summary
This Phase 1/2 study evaluates the safety, feasibility, and preliminary anti-tumor activity of allogeneic donor-derived CAR-NK cells in participants with advanced solid tumors. The CAR target antigen is selected for each participant after tumor profiling using a tissue biopsy and/or liquid biopsy. Participants will receive either a single-target or dual-target CAR-NK product based on the antigen profile.
Detailed description
This is an open-label, biomarker-driven adoptive cell therapy study. Screening / Target Selection (Precision Step): Participants undergo tumor antigen profiling using: Tissue biopsy (preferred when safely feasible), and/or Liquid biopsy (e.g., circulating tumor DNA plus circulating tumor cells/exosome protein assay, as available in the platform). Antigen profiling determines eligibility and assigns participants to: Single-target CAR-NK if one antigen meets positivity thresholds, or Dual-target CAR-NK if two antigens meet thresholds or if heterogeneity is suspected. Pre-specified target menu : TROP2, Mesothelin (MSLN), B7-H3 (CD276), HER2, EGFR, GD2, Claudin18.2, GPC3, PSMA ("Target menu" can be expanded in amendments.) Cell Source / Manufacturing Concept: NK cells are obtained from a healthy allogeneic donor (unrelated or partially matched per site policy). Donor NK cells are collected by leukapheresis, activated/expanded, and genetically modified to express: a single CAR (Arm A) or a dual CAR / dual-target construct (Arm B). Final product is cryopreserved and released after sterility/identity/potency testing. Conditioning & Treatment: Participants receive lymphodepleting chemotherapy followed by CAR-NK infusion(s). Many CAR-NK solid-tumor trials use conditioning regimens such as fludarabine and cyclophosphamide before infusion. Optional cytokine support (e.g., low-dose IL-2) may be used per protocol to support NK persistence, consistent with approaches used in some CAR-NK studies. Follow-up: Intensive safety monitoring during the first 28 days. Tumor imaging at protocol-defined intervals. Correlative studies including CAR-NK persistence and ctDNA dynamics.
Interventions
BIOLOGICALEB-SELECT Single-Target CAR-NK Cells
Donor-derived CAR-NK cells expressing a single CAR selected from the target menu. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion. Similar conditioning drugs are used in CAR-NK solid tumor trials.
BIOLOGICALDual-Target Antigen-Selected CAR-NK
Participants whose profiling identifies two actionable antigens, or strong evidence of antigen heterogeneity. WITH Fludarabine (IV) + Cyclophosphamide (IV), administered prior to CAR-NK infusion . Similar conditioning drugs are used in CAR-NK solid tumor trials.
Sponsors
Essen Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label due to the nature of personalized antigen assignment and cell product differences
Eligibility
Sex/Gender
ALL
Age
8 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years. * Histologically or cytologically confirmed advanced/unresectable or metastatic solid tumor that is relapsed/refractory after standard therapy, or no standard therapy available. * Targetable antigen positivity from the protocol target menu based on: tissue biopsy and/or liquid biopsy platform (as defined in the lab manual). * Arm assignment rules : * Arm A: ≥1 antigen meets "positive" threshold * Arm B: ≥2 antigens meet "positive" threshold * ECOG performance status 0-1 (or 0-2 ). * At least one measurable lesion by RECIST 1.1. * Adequate organ function (hematologic, renal, hepatic, cardiac) within protocol-defined limits. * Willingness to undergo blood draws and required biopsies (when medically feasible). * Negative pregnancy test for participants of childbearing potential; agreement to effective contraception during and after study treatment.
Exclusion criteria
* Prior treatment with gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within a defined washout period . * Active, uncontrolled infection requiring IV antibiotics; known uncontrolled HIV; active HBV/HCV with detectable viral load (per local policy). * Active CNS metastases requiring escalating steroids or urgent intervention (stable treated CNS disease may be allowed ). * Active autoimmune disease requiring systemic immunosuppression, or chronic systemic steroids above protocol threshold. * Clinically significant cardiovascular disease (e.g., recent MI, unstable arrhythmia), uncontrolled pulmonary disease, or other serious comorbidity that increases risk. * Major surgery or anticancer therapy too close to lymphodepletion (protocol-defined washout). * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0 | 28 DAYS |
| Incidence of Dose-Limiting Toxicities (DLTs) | 28 DAYS |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) (RECIST 1.1) | 12 months |
| Disease Control Rate (DCR) | 12 months |
Countries
China
Contacts
CONTACTRhoda M Smith, PHD
Outcome results
None listed