NCT07510828

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

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Advanced or Metastatic Solid Tumors

Interventions

Type	Name	Description
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

Timeline

• Start date: 2026-03-02
• Primary completion: 2027-03-14
• Completion: 2028-04-17
• First posted: 2026-04-06
• Last updated: 2026-04-06

Locations

1 site across 1 country: China