Phase 1/2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors

Study Overview: The study includes two parts. Part A (dose escalation) uses a standard dose-escalation design to evaluate multiple dose levels of EB-NK-301 after lymphodepleting chemotherapy. Part B (dose expansion) enrolls additional participants at the selected RP2D to further characterize safety and to estimate preliminary efficacy within selected tumor-type cohorts.

Treatment Plan: Participants receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by intravenous EB-NK-301 infusions. Participants are monitored closely for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, and other adverse events.

Assessments: Tumor imaging is performed every 8 weeks during the first 12 months, then every 12 weeks as clinically indicated. Blood samples are collected to assess CAR-NK cell persistence, cytokines, and other immune biomarkers.

Follow-up: Participants are followed for safety and survival for up to 24 months after first infusion.

Inclusion criteria

• Age 18 to 75 years at the time of informed consent.
• Histologically or cytologically confirmed advanced or metastatic solid tumor with documented TROP2 expression (per local testing or central confirmation).
• Disease progression on, intolerance to, or ineligibility for available standard therapy.
• At least one measurable lesion per RECIST 1.1.
• ECOG performance status 0 to 1.
• Adequate organ function (hematologic, renal, hepatic) within protocol-defined limits.
• Life expectancy ≥ 12 weeks.
• Willingness to use effective contraception during study participation and for a protocol-defined period after last infusion (if of childbearing potential).
• Ability to understand and willingness to sign written informed consent.

Exclusion criteria

• Active central nervous system (CNS) metastases or leptomeningeal disease (unless treated and clinically stable for ≥ 4 weeks).
• Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
• Uncontrolled active infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.
• Active autoimmune disease requiring systemic immunosuppression.
• Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke within 6 months, uncontrolled arrhythmia).
• Receipt of another investigational agent within 2 weeks (or 5 half-lives, whichever is longer) prior to lymphodepleting chemotherapy.
• Prior gene-modified cellular therapy within 3 months prior to enrollment.
• Systemic corticosteroid therapy > 10 mg/day prednisone equivalent within 7 days prior to lymphodepletion (excluding physiologic replacement).
• Pregnant or breastfeeding.