Advanced Solid Tumors, Metastatic Solid Tumors, TROP2-Expressing Solid Tumors
Conditions
Keywords
Solid tumors, Immunotherapy, Adoptive cell therapy, Natural killer cells, NK cell therapy, CAR-NK, Dose escalation, Dose expansion, TROP2
Brief summary
study evaluates EB-NK-301, an investigational off-the-shelf allogeneic CAR-NK cell product targeting TROP2, in adults with advanced or metastatic solid tumors that express TROP2 and have progressed after standard therapy. The primary goals are to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine a recommended Phase 2 dose (RP2D). Secondary goals include preliminary anti-tumor activity, persistence of infused CAR-NK cells, and exploratory immune biomarkers.
Detailed description
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.
Interventions
BIOLOGICALEB-NK-301
Investigational allogeneic CAR-NK cell product targeting TROP2, administered by intravenous infusion.
DRUGFludarabine
Lymphodepleting chemotherapy administered prior to EB-NK-301 infusion to facilitate immune cell engraftment and persistence.
Sponsors
Beijing Biotech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label study. Participants, investigators, and study staff are aware of the assigned intervention.
Intervention model description
Part A: dose escalation (sequential dose levels). Part B: dose expansion at RP2D in selected tumor cohorts.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) (CTCAE v5.0) | 28 days |
| Incidence and severity of treatment-emergent adverse events (AEs) | 12 months |
| Recommended Phase 2 dose (RP2D) of EB-NK-301 | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) per RECIST 1.1 | 12 months |
| Duration of response (DoR) | 24 months |
| Overall survival (OS) | 24 months |
Countries
China
Contacts
CONTACTshan S Lu, Phd
Outcome results
None listed