RecruitingRecruiting
Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors
NCT07410494 · Essen Biotech
In plain English
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Official title
A Phase 1/2, Open-Label, Biomarker-Driven Study of Allogeneic Donor-Derived CAR-NK Cells With Antigen Selection by Tissue Biopsy and/or Liquid Biopsy Profiling in Participants With Relapsed/Refractory Advanced Solid Tumors (Single-Target vs Dual-Target Strategy)
About this study
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.
Eligibility criteria
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.
Study design
Enrollment target: 85 participants
Allocation: non_randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2026-02-01
Estimated completion: 2028-12-28
Last updated: 2026-02-18
Interventions
Biological: EB-SELECT Single-Target CAR-NK CellsBiological: Dual-Target Antigen-Selected CAR-NK
Primary outcomes
- • Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0 (28 DAYS)
- • Incidence of Dose-Limiting Toxicities (DLTs) (28 DAYS)
Sponsor
Essen Biotech · other
Contacts & investigators
ContactRhoda M Smith, PHD · contact · clinical-trials@essen-biotech.com · +12077706670
All locations (1)
District One HospitalRecruiting
Beijing, Beijing Municipality, China