RecruitingPhase 1Phase 2NCT07410494

Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors

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)

Sponsor

Essen Biotech

Enrollment

85 participants

Start Date

Feb 1, 2026

Study Type

INTERVENTIONAL

Conditions

Breast Cancer Cancer

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.

Eligibility

Min Age: 8 YearsMax Age: 85 Years

Inclusion Criteria12

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 Criteria7

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.

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.