Dual-Target CLDN18.2/HER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma

• 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.