Denne siden ble automatisk oversatt og nøyaktigheten av oversettelsen er ikke garantert. Vennligst referer til engelsk versjon for en kildetekst.

Target-Selected CAR-NK Cells (CD30, CD5, or Mesothelin) for Relapsed/Refractory B2 Thymoma or Thymic Carcinoma (SELECT-NK-THYM)

14. mai 2026 oppdatert av: Beijing Biotech

A Phase 1/2, Open-Label, Target-Selected Study of Allogeneic CAR-NK Cells Directed to CD30, CD5, or Mesothelin in Patients With Relapsed/Refractory B2 Thymoma or Thymic Carcinoma

This Phase 1/2 study evaluates the safety, tolerability, and preliminary efficacy of target-selected CAR-natural killer (CAR-NK) cells in adults with relapsed or refractory B2 thymoma or thymic carcinoma. Participants undergo centralized tumor antigen assessment (CD30, CD5, and mesothelin). Based on the dominant and clinically actionable antigen expression profile, each participant is assigned to one of three parallel cohorts (CD30-CAR-NK, CD5-CAR-NK, or mesothelin-CAR-NK). All cohorts use the same lymphodepleting conditioning regimen followed by CAR-NK infusion(s).

Studieoversikt

Detaljert beskrivelse

This is a first-in-indication, open-label, non-randomized, multi-center Phase 1/2 study with biomarker-driven cohort assignment. Phase 1 (dose escalation): Within each target cohort, a standard 3+3 dose-escalation design evaluates up to three dose levels of the assigned CAR-NK product to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Dose-limiting toxicities (DLTs) are assessed from Day 0 through Day 28 after the first CAR-NK infusion. Phase 2 (dose expansion): After an RP2D is identified in a cohort, an expansion stage enrolls additional participants in that cohort to further characterize safety and estimate preliminary antitumor activity. CAR-NK product: Off-the-shelf, allogeneic cord blood-derived NK cells are genetically modified to express a single-target CAR (anti-CD30, anti-CD5, or anti-mesothelin). The construct includes an IL-15 support element to enhance persistence and an inducible caspase-9 (iCasp9) safety switch for rapid elimination of CAR-NK cells if clinically indicated. Correlative studies: Serial blood and (when feasible) tumor sampling will evaluate CAR-NK persistence, immune activation markers, cytokines, tumor antigen modulation, and exploratory biomarkers of response and resistance. Long-term follow-up: Participants will be followed for delayed adverse events and survival; participants receiving gene-modified cells will also be invited to long-term follow-up consistent with applicable gene therapy guidance.

Studietype

Intervensjonell

Registrering (Antatt)

36

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

    • Guangdong
      • Shenzhen, Guangdong, Kina, 518036
        • Rekruttering
        • Peking University Shenzhen Hospital
        • Ta kontakt med:

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

Inclusion Criteria:

  • Age 18 to 75 years at the time of consent.
  • Histologically confirmed B2 thymoma or thymic carcinoma that is unresectable, metastatic, or recurrent.
  • Relapsed or refractory after at least 1 prior systemic therapy (including a platinum-based regimen for thymic carcinoma when appropriate) or no standard curative option available.
  • Tumor antigen positivity for at least one of the following by central laboratory assessment: CD30, CD5, or mesothelin. Cohort assignment is based on the dominant target (pre-specified algorithm) and feasibility of manufacturing/availability.
  • Measurable disease per RECIST v1.1 (or evaluable disease if measurable disease is not feasible; to be specified).
  • ECOG performance status 0-1 (0-2 may be permitted in expansion at investigator discretion).
  • Adequate organ function: ANC ≥ 1.0 x 10^9/L, platelets ≥ 75 x 10^9/L, hemoglobin ≥ 8 g/dL (transfusions allowed), AST/ALT ≤ 3 x ULN (≤ 5 x ULN with liver involvement), total bilirubin ≤ 1.5 x ULN (except Gilbert's), creatinine clearance ≥ 50 mL/min.
  • Negative pregnancy test for participants of childbearing potential; agreement to use effective contraception.
  • Ability to understand and sign informed consent.

Exclusion Criteria:

  • Active central nervous system involvement by malignancy requiring immediate therapy.
  • Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK) within 90 days or unresolved ≥Grade 2 toxicity from prior cellular therapy.
  • Uncontrolled infection, including active tuberculosis, or uncontrolled hepatitis B or C infection; known uncontrolled HIV infection.
  • Clinically significant autoimmune disease requiring systemic immunosuppression (e.g., >10 mg/day prednisone equivalent) within 14 days of conditioning, except for stable endocrine replacement.
  • Prior allogeneic hematopoietic stem cell transplant with active graft-versus-host disease or ongoing immunosuppression.
  • Significant cardiovascular disease (e.g., NYHA class III/IV heart failure, recent myocardial infarction), uncontrolled arrhythmia, or QTc prolongation felt to increase risk.
  • Pregnancy or breastfeeding.
  • Concurrent participation in another interventional trial with an investigational anticancer agent within 21 days (washout required).
  • Any condition that, in the investigator's judgment, would interfere with safe participation or interpretation of results.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Cohort A: CD30-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

lymfodeplesjon
lymfodeplesjon
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated
Eksperimentell: Cohort B: CD5-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

lymfodeplesjon
lymfodeplesjon
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated
Eksperimentell: Cohort C: Mesothelin-CAR-NK

Lymphodepleting chemotherapy: cyclophosphamide + fludarabine (Days -5 to

-3), followed by CAR-NK infusion on Day 0. A second infusion on Day 7 may be permitted at investigator discretion in Phase 2 if no ≥Grade 3 treatment-related toxicity is observed and product is available.

lymfodeplesjon
lymfodeplesjon
CD30-targeted allogeneic CAR-NK cells
CD5-targeted allogeneic CAR-NK cells
Mesothelin-targeted allogeneic CAR-NK cells
ctivate the iCasp9 safety switch if clinically indicated

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Incidence of Dose-Limiting Toxicities (DLTs)
Tidsramme: 28 Days
DLTs as defined in protocol, assessed during the DLT window after the first CAR-NK infusion. Includes severe infusion-related toxicity, Grade >=3 organ toxicity attributable to CAR-NK cells, severe CRS or neurotoxicity, and treatment-related death.
28 Days
Recommended Phase 2 Dose
Tidsramme: 28 Days
Determined separately for each cohort based on DLTs, overall safety, and pharmacodynamic data
28 Days

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Objective Response Rate
Tidsramme: 12 months
Proportion of participants with complete response (CR) or partial response (PR) per RECIST v1.1 (or modified criteria appropriate for thymic tumors) in each cohort.
12 months
Disease Control Rate
Tidsramme: 12 months
Proportion of participants with CR, PR, or stable disease
12 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

2. mars 2026

Primær fullføring (Antatt)

14. juni 2027

Studiet fullført (Antatt)

17. april 2028

Datoer for studieregistrering

Først innsendt

14. mai 2026

Først innsendt som oppfylte QC-kriteriene

14. mai 2026

Først lagt ut (Faktiske)

20. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

20. mai 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

14. mai 2026

Sist bekreftet

1. mai 2026

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere