PRISM-NK: Precision-Matched Allogeneic Single- or Dual-Target CAR-NK Cells for Advanced Solid Tumors (PRISM-NK)

March 31, 2026 updated by: Beijing Biotech

A Phase 1/2 Biomarker-Guided Platform Study of Allogeneic Donor-Derived Single-Target or Dual-Target CAR-NK Cell Therapy Selected by Tumor Antigen Profiling (Liquid Biopsy and/or Tissue Biopsy) in Participants With Advanced Solid Tumors

This Phase 1/2, open-label, biomarker-guided platform study evaluates the safety, tolerability, and preliminary anti-tumor activity of banked allogeneic donor-derived chimeric antigen receptor natural killer (CAR-NK) cells in adults with advanced solid tumors. During screening, tumor antigen profiling is performed using tissue biopsy and/or liquid biopsy (circulating tumor DNA and/or circulating tumor cells).

Participants are assigned to receive either a single-target CAR-NK product (matched to the dominant tumor antigen) or a dual-target CAR-NK product (matched to two co-expressed antigens) to reduce the risk of antigen escape.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This example trial is designed to reflect common elements of early-phase CAR-NK studies in solid tumors, including dose escalation followed by expansion cohorts, open-label safety monitoring, and response assessment using standard radiologic criteria. Similar solid-tumor CAR-NK studies on ClinicalTrials.gov include trials targeting TROP2 (NCT06066424), NKG2D ligands (NCT03415100), and multi-target CAR-NK platforms that evaluate different antigens such as CLDN6, GPC3, mesothelin, or AXL (NCT05410717).

Antigen selection workflow (precision matching):

  1. Obtain tumor tissue biopsy (preferred) and/or blood for liquid biopsy at screening.
  2. Assess antigen expression using a prespecified panel (example panel: mesothelin, TROP2, HER2, MUC1, CLDN18.2, B7-H3/CD276, AXL, GPC3, CLDN6, EGFR).

  3. Assign participant to: (a) single-target cohort if one antigen meets the threshold; or (b) dual-target cohort if two antigens meet thresholds or if the investigator judges high risk of antigen heterogeneity.

    • Select the matched cryopreserved allogeneic donor-derived CAR-NK product from a manufacturing bank and schedule treatment. Treatment overview: Participants receive lymphodepleting chemotherapy (e.g., fludarabine/cyclophosphamide) followed by one or more infusions of CAR-NK cells. Cytokine support (e.g., low-dose IL-2 or IL-15 agonist per institutional practice) may be given to promote CAR-NK persistence. Participants are monitored closely for cytokine release syndrome (CRS), neurotoxicity, infusion reactions, and other adverse events. Tumor imaging is performed at prespecified intervals during the first 6 months and then less frequently during follow-up.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 to 75 years at the time of consent.
  • Histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory to, relapsed after, or intolerant of standard therapy, or for which no standard therapy exists.
  • At least 1 measurable lesion per RECIST v1.1.
  • Tumor antigen positivity documented by tissue biopsy and/or liquid biopsy using a protocol-specified assay; for dual-target cohort: co-expression of both antigens above threshold.
  • ECOG performance status 0-1.
  • Adequate organ function (hematologic, renal, hepatic) as defined by protocol labs.
  • Ability to undergo lymphodepleting chemotherapy (if required) and receive IV cell infusion.
  • Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception during study participation and for a protocol-defined period after infusion.
  • Willingness to provide baseline blood samples and, when feasible, tumor biopsy for biomarker analyses.

Exclusion Criteria:

  • Active, uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection.
  • Known uncontrolled HIV infection; active hepatitis B or hepatitis C with evidence of active replication (per local testing).
  • Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia) that would increase risk from lymphodepletion or infusion.
  • Active central nervous system (CNS) metastases that are symptomatic or require escalating steroids.

(Stable treated CNS disease may be allowed per protocol.)

  • Current systemic immunosuppressive therapy (e.g., >10 mg/day prednisone equivalent) within a protocol-defined window prior to lymphodepletion.
  • Prior gene-modified cellular therapy within 3 months or any prior therapy that, in the investigator's judgment, would confound safety evaluation.
  • Prior allogeneic hematopoietic stem cell transplant within 6 months, or active graft-versus-host disease.
  • Pregnant or breastfeeding.
  • Any condition that, in the investigator's opinion, would interfere with study participation, compliance, or interpretation of results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Single-target precision-matched CAR-NK
Participants with a single dominant tumor antigen (above a prespecified threshold) receive a matched single-target CAR-NK product manufactured from a healthy donor NK-cell source.
Biological: EB-PT-CAR-NK-S
single-target CAR-NK cell infusion, IV
Biological: EB-PT-CAR-NK-D
dual-target CAR-NK cell infusion, IV
Drug: Lymphodepleting chemotherapy
fludarabine + cyclophosphamide
Drug: Cytokine support
low-dose IL-2 or IL-15 agonist
Experimental: Arm B: Dual-target precision-matched CAR-NK
Participants with co-expression of two target antigens (or high antigen heterogeneity) receive a dual-target CAR-NK product designed to recognize both antigens (e.g., tandem CAR or bicistronic CAR configuration).
Biological: EB-PT-CAR-NK-S
single-target CAR-NK cell infusion, IV
Biological: EB-PT-CAR-NK-D
dual-target CAR-NK cell infusion, IV
Drug: Lymphodepleting chemotherapy
fludarabine + cyclophosphamide
Drug: Cytokine support
low-dose IL-2 or IL-15 agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose- limiting toxicities
Time Frame: 28 days
Dose limiting toxicities refer to specific adverse events or side effects that prevent further dose escalation of an investigational drug or therapy in a clinical trial. DLTs are pre-defined based on severity, duration, and impact on patient safety, typically graded according to established criteria such as the Common Terminology Criteria for Adverse Events (CTCAE). Monitoring DLTs is a critical outcome measure in early-phase (Phase I/II) studies, as it helps determine the maximum tolerated dose (MTD) and guides safe dosing for subsequent trial phases.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

April 17, 2028

Study Registration Dates

First Submitted

March 20, 2026

First Submitted That Met QC Criteria

March 31, 2026

First Posted (Actual)

April 6, 2026

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESBI2026-PRISM-NK-020

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced or Metastatic Solid Tumors

Clinical Trials on EB-PT-CAR-NK-S

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe