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

Phase 2RecruitingNCT07410494

Essen Biotech85 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Interventions

EB-SELECT Single-Target CAR-NK CellsBIOLOGICAL

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.

Dual-Target Antigen-Selected CAR-NKBIOLOGICAL

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.

Eligibility

Sex: ALLMin age: 8 YearsMax age: 85 Years

Medical Language ↔ Plain English

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 if desired in your program). * 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 (or ever, depending on your protocol). * 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 if you choose). * 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.

Outcomes

Primary Outcomes

Incidence, type, and severity of adverse events (AEs), graded by CTCAE v5.0

Time frame: 28 DAYS

Incidence of Dose-Limiting Toxicities (DLTs)

Time frame: 28 DAYS

Secondary Outcomes

Objective Response Rate (ORR) (RECIST 1.1)

Time frame: 12 months

Disease Control Rate (DCR)