- ICH GCP
- Register voor klinische proeven in de VS.
- Klinische proef NCT07617753
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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studiecontact
- Naam: Seni S Lu, Phd
- Telefoonnummer: +86 13076790030
- E-mail: Seni-Lu@beijing-biotech.com
Studie Locaties
-
-
Guangdong
-
Shenzhen, Guangdong, China, 518036
- Werving
- Peking University Shenzhen Hospital
-
Contact:
- Zhen J Peng, Phd
- Telefoonnummer: +86 13076790039
- E-mail: Zhen-Peng@beijing-biotech.com
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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.
|
|
Experimenteel: 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.
|
|
Experimenteel: 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.
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
Incidentie van dosisbeperkende toxiciteiten (DLT's)
Tijdsspanne: 28 Dagen
|
28 Dagen
|
|
Incidence and severity of treatment-emergent adverse events (TEAEs) graded by CTCAE v5.0
Tijdsspanne: 12 months
|
12 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
|
Duur van respons (DOR) onder responders
Tijdsspanne: 12 maanden
|
12 maanden
|
|
Objective response rate (ORR) by RECIST v1.1
Tijdsspanne: 6 months
|
6 months
|
Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Urogenitale ziekten
- Genitale ziekten
- Endocriene systeemziekten
- Pathologische processen
- Urogenitale neoplasmata
- Neoplasmata per site
- Neoplasmata
- Vrouwelijke urogenitale ziekten
- Vrouwelijke urogenitale ziekten en zwangerschapscomplicaties
- Ziekte attributen
- Neoplasmata per histologisch type
- Genitale ziekten, vrouw
- Endocriene klierneoplasmata
- Neoplasmata, glandulair en epitheel
- Ovariële ziekten
- Adnexale ziekten
- Genitale neoplasmata, vrouwelijk
- Gonadale aandoeningen
- Carcinoom
- Ziekten van de eileiders
- Pathologische aandoeningen, tekenen en symptomen
- Carcinoom, ovariumepitheel
- Herhaling
- Ovariumneoplasmata
- Eileiderneoplasmata
- Organische chemicaliën
- Therapeutica
- Koolwaterstoffen
- Patiëntenzorg
- Gezondheidsdiensten
- Gezondheidszorgfaciliteiten personeel en diensten
- Fosforamide mosterd
- Stikstofmosterdverbindingen
- Mosterdverbindingen
- Koolwaterstoffen, gehalogeneerd
- Fosforamides
- Organofosforverbindingen
- Cyclofosfamide
- Palliatieve zorg
Andere studie-ID-nummers
- EB-CARNK-OV-110
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .