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NCT Number: NCT07410494

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

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.

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Key information

Conditions

Cancer Acute Myeloid Leukemia (AML) Adenocarcinoma Adnexal Diseases Astrocytoma Blood Protein Disorders Breast Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Cardiovascular Diseases Colonic Diseases Colorectal Cancer (Locally Advanced or Metastatic) Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Diseases, Male Genital Neoplasms, Female Genital Neoplasms, Male Glioblastoma Glioma Gonadal Disorders Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Intestinal Diseases Intestinal Neoplasms Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Liver Cancer Liver Diseases Liver Neoplasms Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Melanoma Melanoma (Skin Cancer) Multiple Myeloma Multiple Myeloma (MM), Lymphoma, Large B-Cell, Diffuse (DLBCL), Lymphoma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Plasma Cell Neoplastic Processes Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non Hodgkin Lymphoma Non-small Cell Lung Cancer (NSCLC) Ovarian Cancer Ovarian Diseases Ovarian Neoplasms Pancreatic Ductal Adenocarcinoma (PDAC) Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Prostate Cancer - Recurrent Prostatic Diseases Prostatic Neoplasms Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Vascular Diseases

Age range

8 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

District One Hospital

Beijing, Beijing Municipality, 086-373, China

Location status: Recruiting

Location contact

SAMI XI, MD

CONTACT

[email protected]

+14012275001

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

EB-SELECT Single-Target CAR-NK Cells

Biological

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.

Other names: Lymphodepleting Chemotherapy, Fludarabine, Cyclophosphamide, IL-2

Dual-Target Antigen-Selected CAR-NK

Biological

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.

Other names: EB-SELECT Dual-Target CAR-NK Cells, Fludarabine, Cyclophosphamide, IL-2

Primary outcomes

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

    Time frame: 28 DAYS

  2. Incidence of Dose-Limiting Toxicities (DLTs)

    Time frame: 28 DAYS

Secondary outcomes

  1. Objective Response Rate (ORR) (RECIST 1.1)

    Time frame: 12 months

  2. Disease Control Rate (DCR)

    Time frame: 12 months

Study contacts

Contact information is provided by the study sponsor or research team.

Rhoda M Smith, PHD

CONTACT

[email protected]

+12077706670

Sponsors and collaborators

Lead sponsor

Essen Biotech

Other

Registry information

Official study 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)

Acronym: SELECT-CAR-NK

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Feb 13, 2026
Registry last updated
Feb 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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