This example study evaluates the safety, feasibility, cellular kinetics, and preliminary anti-tumor activity of EBNK-1822H2, an illustrative allogeneic cord blood-derived dual-target CAR-NK cell product directed against CLDN18.2 and HER2, in adults with relapsed/refractory or metastatic esophageal adenocarcinoma after standard therapy. The study uses dose escalation followed by biomarker-defined expansion and prospectively records EGFR expression as an exploratory biomarker of antigen escape.
Background and target-selection logic. Esophageal adenocarcinoma shares biomarker biology with GEJ adenocarcinoma. In the current public development landscape, CLDN18.2 and HER2 are the two most clinically actionable candidates for a first esophageal adenocarcinoma dual-target CAR-NK concept. This example therefore advances a CLDN18.2/HER2 tandem-target product and treats EGFR as a pre-specified exploratory biomarker, not as the primary CAR target in version 1. Investigational product. EBNK-1822H2 is a hypothetical off-the-shelf NK-cell product derived from cord blood and engineered with a tandem CAR recognizing CLDN18.2 and HER2, together with a persistence-support module (for example, membrane-bound IL-15) and an inducible caspase-9 safety switch. This is an example investigational product description for protocol-drafting purposes only. Study structure. Phase 1 uses an open-label dose-escalation design after fludarabine/cyclophosphamide lymphodepletion to identify the maximum tolerated dose (MTD) and recommended phase 2 dose/schedule (RP2D/RP2S). Phase 2 expands at the selected regimen in three biomarker-defined strata: (1) CLDN18.2-positive/HER2-negative, (2) HER2-positive/CLDN18.2-low or negative, and (3) dual-positive disease. Participants receive one intravenous infusion on Day 0; a protocol-defined repeat infusion on Day 21 may be allowed in the expansion portion if there is no DLT or uncontrolled grade 3+ immune toxicity. Correlative program. Screening includes central or local assessment of CLDN18.2 and HER2, with EGFR captured prospectively at baseline and, when feasible, at progression. Correlative studies include ctDNA response, cytokine profiling, CAR-NK persistence, tumor microenvironment markers, and antigen-pattern analyses to inform future multi-target program evolution.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.
Lymphodepletion backbone
Lymphodepletion backbone
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China
RECRUITINGIncidence of dose-limiting toxicities (DLTs)
Time frame: 28 days
Incidence and severity of treatment-emergent adverse events
Time frame: 12 months
Recommended phase 2 dose
Time frame: 6 months
Objective response rate (ORR) by RECIST v1.1
Time frame: 12 months
Disease control rate (DCR) by RECIST v1.1
Time frame: 12 months
Duration of response
Time frame: 12 Months
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