Dual-Target HER2/CEA CAR-NK Cells in Advanced Biliary Tract Cancer (DUET-BTC)
A Phase 1/2, Open-Label, Biomarker-Selected Study of Allogeneic Dual-Target HER2/CEACAM5 Chimeric Antigen Receptor Natural Killer Cells (EB-HC01) in Participants With Unresectable or Metastatic Cholangiocarcinoma and Other Biliary Tract Cancers
調査の概要
詳細な説明
Biliary tract cancers remain highly lethal after progression on gemcitabine/platinum-based therapy, and only a biomarker-defined minority have actionable cell-surface targets.
HER2 has the strongest clinical validation among the antigens under consideration, including active HER2-targeted drug development and prior HER2 CAR-T experience in advanced BTC. CEACAM5 is retained as a complementary second target because it may reduce antigen escape and improve coverage of heterogeneous disease; however, it is treated conservatively because prior CEA-directed cell therapy has shown gastrointestinal and pulmonary toxicity in other solid tumors. EpCAM is not used for enrollment in this example because physiologic expression in the biliary tree may narrow the safety window for a first systemic study. EB-HC01 is designed as an off-the-shelf cord bloodderived NK-cell product manufactured as a fixed 1:1 mixture of HER2-CAR-NK and CEACAM5-CAR-NK cells.
After fludarabine/cyclophosphamide lymphodepletion, participants receive intravenous EB-HC01 on Days 0 and 7 of a 28-day cycle. In Part A, a standard 3+3 doseescalation design evaluates 3 flat-dose levels to identify the RP2D. In Part B, an expansion cohort at RP2D better defines safety and preliminary activity in biomarkerconfirmed dual-positive BTC.
Key correlative studies include central HER2 and CEACAM5 testing, ctDNA analysis, serum CA19-9 and CEA,and serial blood assessments of CAR-NK persistence and cytokine kinetics. EpCAM testing is retained as an exploratory biomarker to inform future protocol amendments but is not used to determine eligibility.
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：Seni 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 or cytologically confirmed unresectable, recurrent, or metastatic intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder carcinoma.
- Disease progression after at least 1 prior gemcitabine/platinum-containing regimen in the advanced setting; prior durvalumab and prior HER2-targeted therapy are allowed.
- Central biomarker confirmation of HER2 positivity (IHC 3+ or IHC 2+/ISH+ or ERBB2 amplification) and CEACAM5/CEA positivity (membranous expression in >=20% of viable tumor cells by IHC).
- At least 1 measurable lesion according to RECIST 1.1.
- ECOG performance status 0-1.
- Adequate marrow, renal, hepatic, and cardiac function as defined by the protocol.
- Resolved biliary obstruction or stable internal/external drainage for >=7 days before lymphodepletion, with no active cholangitis.
- Life expectancy >=12 weeks.
- Willingness to provide archival or fresh tumor tissue and serial blood samples for central biomarker testing and correlative studies.
- Agreement to use protocol-specified contraception
Exclusion Criteria:
- Prior HER2-directed or CEA-directed gene-modified cell therapy.
- Untreated or unstable CNS metastases or leptomeningeal disease.
- Active uncontrolled infection, including uncontrolled cholangitis, sepsis, or clinically significant uncontrolled hepatitis or HIV infection.
- Ongoing systemic immunosuppression greater than 10 mg/day prednisone equivalent within 7 days before lymphodepletion.
- Clinically significant interstitial lung disease, uncontrolled heart failure, unstable arrhythmia, or recent myocardial infarction.
- Child-Pugh B or C liver disease, hepatic encephalopathy, or clinically significant refractory ascites.
- Prior allogeneic solid organ transplant or allogeneic stemcell transplant.
- Active autoimmune disease requiring systemic therapy within the previous 2 years.
- Pregnancy or breastfeeding.
- Any condition that, in the investigator's judgment, would make lymphodepletion or EB-HC01 infusion unsafe or would interfere with protocol compliance.
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：非ランダム化
- 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：EB-HC01 after lymphodepletion
Participants with biomarker-confirmed HER2/CEACAM5-positive advanced biliary tract cancer receive fludarabine plus cyclophosphamide on Days -5 to -3, followed by EB-HC01 intravenously on Days 0 and 7 of each 28-day cycle.
Up to 2 cycles are permitted during doseescalation and up to 4 cycles are allowed in expansion in the absence of progression or prohibitive toxicity.
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フルダラビン
シクロホスファミド
EB-HC01 dual-target CARNK cells
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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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Dose-Limiting Toxicities
時間枠：28 Days
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28 Days
|
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Treatment-Emergent Adverse Events
時間枠：12 months
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12 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
全生存
時間枠：24ヶ月
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24ヶ月
|
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客観的回答率
時間枠：12ヶ月
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12ヶ月
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反応期間
時間枠：24ヶ月
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24ヶ月
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無増悪生存
時間枠：24か月
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24か月
|
|
Disease Control Rate
時間枠：12 months
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12 months
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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
- ESBI2026-306
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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