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

Official title

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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Dose- limiting toxicities [Time frame: 28 days]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Shenzhen Hospital — Shenzhen

Identifiers

NCT: NCT07510828 · ESBI2026-PRISM-NK-020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗