Advanced or Metastatic Solid Tumors
Conditions
Keywords
allogeneic NK cells, solid tumor, CAR-NK, mesothelin, tumor
Brief 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.
Interventions
BIOLOGICALEB-PT-CAR-NK-S
single-target CAR-NK cell infusion, IV
BIOLOGICALEB-PT-CAR-NK-D
dual-target CAR-NK cell infusion, IV
fludarabine + cyclophosphamide
DRUGCytokine support
low-dose IL-2 or IL-15 agonist
Sponsors
Beijing Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label due to the nature of cell therapy administration and the need for real-time safety monitoring.
Intervention model description
Biomarker-guided platform design. Participants are assigned based on tumor antigen profiling to receive either a single-target or dual-target CAR-NK product. Phase 1 uses a standard 3+3 dose-escalation design within each arm to identify the recommended Phase 2 dose (RP2D). Phase 2 includes target-specific expansion cohorts at the RP2D to estimate preliminary efficacy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose- limiting toxicities | 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. |
Countries
China
Contacts
CONTACTshan S Lu, Phd
Outcome results
None listed