Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

Dual-Targeting CAR-NK Cells for Recurrent Ovarian Cancer (MSLN, FRα, MUC16) pt2 (DUAL-OV-CAR-NK)

25. maj 2026 opdateret af: Beijing Biotech

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

This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of dual-targeting chimeric antigen receptor natural killer (CAR-NK) cells in participants with recurrent or refractory epithelial ovarian, primary peritoneal, or fallopian tube cancer. At screening, each participant's tumor is assessed for expression of Mesothelin (MSLN), Folate Receptor alpha (FRalpha/FOLR1), and MUC16 (CA 125). Participants are assigned to the dual-target CAR-NK product that best matches their tumor antigen profile to reduce the risk of antigen escape.

Studieoversigt

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

36

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

    • Guangdong
      • Shenzhen, Guangdong, Kina, 518036
        • Rekruttering
        • Peking University Shenzhen Hospital
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Eksperimentel: 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.
Eksperimentel: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Forekomst af dosisbegrænsende toksiciteter (DLT'er)
Tidsramme: 28 dage
28 dage
Incidence and severity of treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0
Tidsramme: 12 months
12 months

Sekundære resultatmål

Resultatmål
Tidsramme
Varigheden af respons (DOR) blandt respondenter
Tidsramme: 12 måneder
12 måneder
Objective response rate (ORR) by RECIST v1.1
Tidsramme: 6 months
6 months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. marts 2026

Primær færdiggørelse (Anslået)

14. juni 2027

Studieafslutning (Anslået)

17. marts 2028

Datoer for studieregistrering

Først indsendt

25. maj 2026

Først indsendt, der opfyldte QC-kriterier

25. maj 2026

Først opslået (Faktiske)

1. juni 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

1. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

25. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Epitelial ovariecancer

Kliniske forsøg med Dual-target CAR-NK cell product

Abonner