Dual-Target CLDN18.2/HER2 CAR-NK Cells for Advanced Esophageal Adenocarcinoma
A Phase 1/2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target CLDN18.2/HER2 Chimeric Antigen Receptor Natural Killer Cells (EBNK-1822H2) in Adults With Relapsed, Refractory, or Metastatic Esophageal Adenocarcinoma
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：shan S Lu, Phd
- 電話番号：+86 13076790030
- メール：Seni-Lu@beijing-biotech.com
研究場所
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Guangdong
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Shenzhen、Guangdong、中国、518036
- 募集
- Peking University Shenzhen Hospital
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コンタクト：
- Zhen J Peng, Phd
- 電話番号：+86 13076790039
- メール：Zhen-Peng@beijing-biotech.com
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：EBNK-1822H2 after lymphodepletion
Participants receive fludarabine and cyclophosphamide lymphodepletion followed by intravenous infusion of allogeneic dual-target CLDN18.2/HER2
CAR-NK cells on Day 0. A protocol-defined repeat infusion on Day 21 may be permitted in dose expansion if safety criteria are met.
|
Illustrative allogeneic cord blood-derived NK-cell product engineered to recognize CLDN18.2 and HER2.
他の名前：
Lymphodepletion backbone
他の名前：
Lymphodepletion backbone
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
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用量制限毒性（DLT）の発生率
時間枠：28日間
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28日間
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Incidence and severity of treatment-emergent adverse events
時間枠：12 months
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12 months
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Recommended phase 2 dose
時間枠：6 months
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6 months
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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RECIST v1.1による客観的奏効率（ORR）
時間枠：12ヶ月
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12ヶ月
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Disease control rate (DCR) by RECIST v1.1
時間枠：12 months
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12 months
|
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Duration of response
時間枠：12 Months
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12 Months
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- EBNK-EAC-1822H2-116
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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