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Dual-target CLDN18.2/HER2 CAR-NK Cells for Advanced Gastric/GEJ Cancer

ConditionsAdvanced Gastric AdenocarcinomaAdvanced Gastroesophageal Junction Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorBeijing Biotech

About this trial

This example planning study proposes a phase 1/2 evaluation of an allogeneic, cord-blood-derived dual-target CAR-NK product directed against CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma after prior standard systemic therapy. CLDN18.2 is selected as the anchor antigen because it has the more disease-specific gastric/GEJ cell-therapy development footprint, while HER2 is retained as the complementary second antigen to address co-expressing or heterogeneous disease. Phase 1 uses a 3+3 dose-escalation design after fludarabine/cyclophosphamide lymphodepletion followed by three intravenous CAR-NK infusions on Days 0, 3, and 7. Phase 2 expansion evaluates the recommended phase 2 dose and preliminary antitumor activity

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Signed informed consent before any study-specific procedure.

Age 18 to 75 years.

Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+/ISH+ using gastric/GEJ testing criteria.

Disqualifiers

Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).

Active or untreated central nervous system metastases or leptomeningeal disease.

Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.

Active autoimmune disease requiring systemic immunosuppression.

Trial design

Design model

Sequential

Treatments tested in this trial

  • EB-DT-CAR-NK

    Biological/Vaccine

    Allogeneic, cord-blood-derived CAR-NK cells engineered to target CLDN18.2 and HER2 (ERBB2). Planned phase 1 dose levels: 2 x 10\^6, 4 x 10\^6, and 8 x 10\^6 cells/kg/infusion. Administered intravenously on Days 0, 3, and 7.

  • Fludarabine

    Drug

    Lymphodepleting chemotherapy administered intravenously at 30 mg/m\^2/day on Days -5 to -3.

  • Cyclophosphamide

    Drug

    Lymphodepleting chemotherapy administered intravenously at 500 mg/m\^2/day on Days -5 to -3.

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: Dose Escalation CohortExperimental treatment 3 interventions
Group B: Dose Expansion CohortExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose-limiting toxicities (DLTs)

DLTs graded by CTCAE v5.0, with CRS and ICANS graded using ASTCT criteria.

Time frame
28 days
2

Determination of MTD

Dose-escalation decision based on DLT frequency and overall tolerability across planned cohorts.

Time frame
6 months
3

Objective response rate (ORR)

Confirmed complete response plus partial response according to RECIST v1.1 in evaluable subjects in the expansion cohort.

Time frame
12 months

Secondary outcomes

1

Progression-free survival (PFS)

Time from first infusion to disease progression or death from any cause.

Time frame
12 months
2

Overall survival (OS)

Time from first infusion to death from any cause.

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Beijing Biotech

Lead sponsor

Source ClinicalTrials.gov
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