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

14 maj 2026 uppdaterad 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).

Studieöversikt

Detaljerad beskrivning

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.

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:

  • 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

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: 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.

lymfodpletion
lymfodpletion
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
Experimentell: 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.

lymfodpletion
lymfodpletion
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
Experimentell: 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.

lymfodpletion
lymfodpletion
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

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Incidence of Dose-Limiting Toxicities (DLTs)
Tidsram: 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
Tidsram: 28 Days
Determined separately for each cohort based on DLTs, overall safety, and pharmacodynamic data
28 Days

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Objective Response Rate
Tidsram: 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
Tidsram: 12 months
Proportion of participants with CR, PR, or stable disease
12 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 april 2028

Studieregistreringsdatum

Först inskickad

14 maj 2026

Först inskickad som uppfyllde QC-kriterierna

14 maj 2026

Första postat (Faktisk)

20 maj 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

20 maj 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 maj 2026

Senast verifierad

1 maj 2026

Mer information

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