Dual-target CLDN18.2/HER2 CAR-NK cells for advanced esophageal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This early-phase study uses a dose-escalation design to determine the maximum tolerated dose and RP2D for an off-the-shelf cord blood–derived dual-target CAR-NK product, given after lymphodepletion. It includes three biomarker-defined expansion cohorts to explore activity in CLDN18.2-positive/HER2-negative, HER2-positive/CLDN18.2-low, and dual-positive disease, with a potential second infusion on day 21 if safety allows. The program also prospectively examines biomarker data, including EGFR, as an exploratory indicator of antigen escape. Safety, feasibility, cellular kinetics, and preliminary anti-tumor activity are the primary signals of interest.

Why it matters

Who can join: the full rules

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.

Where it's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: shan S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.