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

NCT07598955 | Recruiting Phase 1 DMC

• 1 other identifier: EB-CARNK-THYM-009
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

B2 Thymoma; Thymic Carcinoma

Keywords

CAR-NK; Natural killer cells; Adoptive cell therapy; Thymic epithelial tumor; CD30; CD5; Mesothelin; Biomarker-guided; Solid tumor immunotherapy

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicities (DLTs)

  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

  Determined separately for each cohort based on DLTs, overall safety, and pharmacodynamic data

  28 Days

Secondary Outcomes (2)

• Objective Response Rate

  12 months

• Disease Control Rate

  12 months

Study Arms (3)

Cohort A: CD30-CAR-NK

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: EB-CAR30-NK; Biological: EB-CAR5-NK; Biological: EB-CARMSLN-NK; Drug: Rimiducid (AP1903)

Cohort B: CD5-CAR-NK

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: EB-CAR30-NK; Biological: EB-CAR5-NK; Biological: EB-CARMSLN-NK; Drug: Rimiducid (AP1903)

Cohort C: Mesothelin-CAR-NK

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: EB-CAR30-NK; Biological: EB-CAR5-NK; Biological: EB-CARMSLN-NK; Drug: Rimiducid (AP1903)

Interventions

Cyclophosphamide DRUG

lymphodepletion

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

Fludarabine DRUG

lymphodepletion

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

EB-CAR30-NK BIOLOGICAL

CD30-targeted allogeneic CAR-NK cells

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

EB-CAR5-NK BIOLOGICAL

CD5-targeted allogeneic CAR-NK cells

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

EB-CARMSLN-NK BIOLOGICAL

Mesothelin-targeted allogeneic CAR-NK cells

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

Rimiducid (AP1903) DRUG

ctivate the iCasp9 safety switch if clinically indicated

Cohort A: CD30-CAR-NK; Cohort B: CD5-CAR-NK; Cohort C: Mesothelin-CAR-NK

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Thymoma; Thymic epithelial tumor

Interventions

Cyclophosphamide; fludarabine; AP 1903 reagent

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Thymus Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study; participants and investigators know the assigned cohort and treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to one of three CAR-NK target cohorts based on centralized tumor antigen expression testing (CD30, CD5, mesothelin). Each cohort uses a Phase 1 dose-escalation stage followed by a Phase 2 expansion stage.

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: May 20, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): April 17, 2028
• Last Updated: May 20, 2026

Record last verified: 2026-05

Locations

CN (1)