Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16) pt2 (DUAL-OV-CAR-NK)
A Phase 1/2, Open-Label, Biomarker-Assigned Study of Dual-Targeting CAR-NK Cells Directed Against Mesothelin (MSLN), Folate Receptor Alpha (FRα/FOLR1), and/or MUC16 (CA125) in Patients With Recurrent or Refractory High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
調査の概要
状態
詳細な説明
The study has two parts: (1) dose escalation using a standard 3+3 design within each antigen-pair cohort to determine safety and a recommended Phase 2 dose (RP2D), and (2) dose expansion at the RP2D to explore preliminary efficacy and translational biomarkers.
Target selection (biomarker assignment): Tumor tissue (archival or fresh biopsy) is evaluated by immunohistochemistry (IHC) and/or flow cytometry for MSLN, FRalpha, and MUC16.
Eligibility requires expression of at least two of the three targets above a pre-specified threshold. If all three are positive, a Target Selection Committee assigns the participant to the dual-target pair with the highest combined expression (e.g., H-score or percent positive cells) and acceptable normal-tissue risk.
Treatment schema: Participants receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) followed by CAR-NK administration. In this example, CAR-NK cells are given intraperitoneally via an implanted port to maximize exposure to peritoneal disease, with optional intravenous dosing per investigator judgment. Participants are monitored closely for cytokine release syndrome (CRS), neurotoxicity (ICANS), cytopenias, infections, and other adverse events.
Response assessments are performed by RECIST v1.1 at regular intervals, with CA 125 trends collected as supportive disease activity data. Follow-up: Participants are followed for adverse events through 12 months and for survival for up to 24 months. Long-term follow-up for gene-modified cell therapy safety may be required per local regulations.
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
-
-
Guangdong
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Shenzhen、Guangdong、中国、518036
- 募集
- Peking University Shenzhen Hospital
-
コンタクト:
- Zhen J Peng, Phd
- 電話番号:+86 13076790039
- メール:Zhen-Peng@beijing-biotech.com
-
-
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 epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (high-grade serous preferred).
- Recurrent or refractory disease after at least 2 prior systemic treatment lines (including a platinum-based regimen unless contraindicated).
- Measurable disease per RECIST v1.1.
- Tumor expresses at least two of the following targets above protocol-defined threshold: MSLN, FRalpha (FOLR1), MUC16 (CA 125) (archival or fresh biopsy).
- ECOG performance status 0-1.
- Adequate organ function : ANC >= 1.0 x 10^9/L; platelets >= 75 x 10^9/L; hemoglobin >= 8 g/dL; AST/ALT <= 3 x ULN (<= 5 x ULN with liver metastases); total bilirubin <= 1.5 x ULN; creatinine clearance >= 50 mL/min.
- Negative pregnancy test for women of childbearing potential; agreement to use effective contraception through 12 months post-infusion (or per local gene-therapy guidance).
- Able to comply with study procedures and follow-up schedule; written informed consent.
Exclusion Criteria:
- Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 6 months (or any prior therapy directed to the same target, per protocol).
- Active central nervous system (CNS) metastases or carcinomatous meningitis requiring therapy.
- Uncontrolled infection, including active tuberculosis; or clinically significant, uncontrolled viral infection.
- Known HIV infection with uncontrolled viremia; active hepatitis B or hepatitis C with detectable viral load (testing required at screening).
- Clinically significant cardiovascular disease (e.g., recent myocardial infarction, uncontrolled arrhythmia, NYHA Class III/IV heart failure).
- Active autoimmune disease requiring systemic immunosuppression within 30 days (physiologic steroid replacement allowed).
- Concurrent anti-cancer therapy (chemotherapy, targeted therapy, radiotherapy) not permitted within a protocol-defined washout period.
- Major surgery within 4 weeks prior to lymphodepletion (except minor procedures)
- Pregnant or breastfeeding.
- Any condition that, in the investigator's judgment, would increase risk (e.g., severe pulmonary disease) or interfere with study interpretation.
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:並列代入
- 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-NK-MF
Dual-target CAR-NK cells recognizing Mesothelin (MSLN) and Folate Receptor alpha (FRalpha/FOLR1).
Assigned to participants whose tumors express MSLN and FRalpha above threshold
|
EB-NK-MF CAR-NK cells (dose levels 1-3)
Cyclophosphamide + Fludarabine lymphodepletion
Standard supportive care (e.g., antimicrobial prophylaxis) per institutional practice.
|
|
実験的:EB-NK-MM
Dual-target CAR-NK cells recognizing Mesothelin (MSLN) and MUC16 (CA 125).
Assigned to participants whose tumors express MSLN and MUC16 above threshold.
|
EB-NK-MF CAR-NK cells (dose levels 1-3)
Cyclophosphamide + Fludarabine lymphodepletion
Standard supportive care (e.g., antimicrobial prophylaxis) per institutional practice.
|
|
実験的:EB-NK-FM
Dual-target CAR-NK cells recognizing FRalpha (FOLR1) and MUC16 (CA 125).
Assigned to participants whose tumors express FRalpha and MUC16 above threshold.
|
EB-NK-MF CAR-NK cells (dose levels 1-3)
Cyclophosphamide + Fludarabine lymphodepletion
Standard supportive care (e.g., antimicrobial prophylaxis) per institutional practice.
|
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 |
|---|---|
|
用量制限毒性(DLT)の発現率
時間枠:28日
|
28日
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0
時間枠:12 months
|
12 months
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
応答者における反応継続期間(DOR)
時間枠:12ヶ月
|
12ヶ月
|
|
Objective response rate (ORR) by RECIST v1.1
時間枠:6 months
|
6 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
- 泌尿生殖器疾患
- 生殖器疾患
- 内分泌系疾患
- 病理学的プロセス
- 泌尿生殖器腫瘍
- 部位別新生物
- 新生物
- 女性の泌尿生殖器疾患
- 女性の泌尿生殖器疾患と妊娠合併症
- 疾患の属性
- 組織型別の新生物
- 生殖器疾患、女性
- 内分泌腺腫瘍
- 新生物、腺および上皮
- 卵巣疾患
- 付属器疾患
- 性器腫瘍、女性
- 性腺疾患
- がん
- 卵管疾患
- 病理学的状態、徴候および症状
- がん、卵巣上皮
- 再発
- 卵巣腫瘍
- 卵管腫瘍
- 有機化学物質
- 治療
- 炭化水素
- 患者ケア
- 医療サービス
- 医療施設の労働力とサービス
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- シクロホスファミド
- 緩和ケア
その他の研究ID番号
- EB-CARNK-OV-110
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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