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

25 maj 2026 uppdaterad av: 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.

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

36

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studieorter

    • Guangdong
      • Shenzhen, Guangdong, Kina, 518036

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Nej

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Experimentell: 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.
Experimentell: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Tidsram
Förekomst av dosbegränsande toxiciteter (DLT)
Tidsram: 28 dagar
28 dagar
Incidence and severity of treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0
Tidsram: 12 months
12 months

Sekundära resultatmått

Resultatmått
Tidsram
Varaktighet av respons (DOR) bland respondenter
Tidsram: 12 månader
12 månader
Objective response rate (ORR) by RECIST v1.1
Tidsram: 6 months
6 months

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

2 mars 2026

Primärt slutförande (Beräknad)

14 juni 2027

Avslutad studie (Beräknad)

17 mars 2028

Studieregistreringsdatum

Först inskickad

25 maj 2026

Först inskickad som uppfyllde QC-kriterierna

25 maj 2026

Första postat (Faktisk)

1 juni 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

1 juni 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

25 maj 2026

Senast verifierad

1 maj 2026

Mer information

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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