Recruiting
Phase 1/2
Dual-Target CLDN18.2/HER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma
Condition(s) studied
Recurrent or Metastatic Esophageal AdenocarcinomaBiomarker-selected CLDN18.2-positive and/or HER2-positive Disease
Investigational drug(s) / intervention(s)
EBNK-1822H2 dual-target CLDN18.2/HER2 CAR-NK cells: Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.
Fludarabine: Lymphodepletion backbone
Cyclophosphamide: Lymphodepletion backbone
Study summary
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.
Eligibility
Inclusion Criteria:
* Histologically confirmed esophageal adenocarcinoma or Siewert I/II gastroesophageal junction adenocarcinoma judged biologically consistent with esophageal adenocarcinoma, unresectable/recurrent/metastatic, and not amenable to curative therapy.
* Disease progressed after at least 1 prior systemic regimen for advanced disease, or the participant is intolerant of / ineligible for standard therapy. Biomarker-directed therapy must have been received or deemed inappropriate/unavailable where standard in the local setting.
* At least 1 measurable lesion by RECIST v1.1.
* Evidence of at least one selected target: CLDN18.2-positive by validated IHC (example threshold: membranous staining in
≥75% of tumor cells with moderate/strong intensity or protocol-specified central threshold), and/or HER2-positive by IHC 3+ or IHC 2+/ISH-amplified disease.
* ECOG performance status 0-1.
* Adequate marrow, renal, hepatic, pulmonary, and cardiac function per protocol laboratory thresholds.
* Life expectancy ≥12 weeks.
* Resolution of clinically significant prior-therapy toxicities to grade ≤1 (except alopecia or stable endocrinopathies).
* Willingness to provide archival tumor tissue and to undergo fresh biopsy when safely feasible.
* Negative pregnancy test for participants of childbearing potential and agreement to protocol-defined contraception.
Exclusion Criteria:
* Esophageal squamous cell carcinoma or non-adenocarcinoma histology.
* Known active CNS metastases or leptomeningeal disease; previously treated stable CNS disease may be allowed only if asymptomatic and off escalating steroids per protocol.
* Prior gene-modified cellular therapy within 12 weeks, or another investigational therapy likely to confound interpretation of safety or efficacy.
* Active uncontrolled infection, including uncontrolled hepatitis B, hepatitis C, HIV viremia, sepsis, or clinically significant opportunistic infection.
* Ongoing systemic immunosuppressive therapy above physiologic steroid replacement.
* Active autoimmune disease requiring systemic treatment within 2 years.
* Clinically significant interstitial lung disease/pneumonitis, uncontrolled cardiovascular disease, or left ventricular ejection fraction \<50%.
* Active gastrointestinal perforation, uncontrolled bleeding, or clinically significant mucosal ulceration that would increase study-treatment risk.
* Prior solid organ transplant or active graft-versus-host disease.
* Pregnant or breastfeeding.
* Another active malignancy requiring systemic therapy, except protocol-permitted low-risk cancers.
Primary outcome measure(s)
- Incidence of dose-limiting toxicities (DLTs) — 28 days
- Incidence and severity of treatment-emergent adverse events — 12 months
- Recommended phase 2 dose — 6 months
Trial sites (1)
| Facility | City | Region | Status |
| Peking University Shenzhen Hospital |
Shenzhen |
Guangdong |
Recruiting |
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