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

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.

Eligibility

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.

Conditions2

Interventions4

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