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

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).

Study Overview

• Status: Recruiting
• Conditions: Thymic Carcinoma; B2 Thymoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: EB-CAR30-NK; Biological: EB-CAR5-NK; Biological: EB-CARMSLN-NK; Drug: Rimiducid (AP1903)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Seni S Lu, Phd; Phone Number: +86 13076790030; Email: Seni-Lu@beijing-biotech.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Zhen J Peng, Phd; Phone Number: +86 13076790039; Email: Zhen-Peng@beijing-biotech.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Cyclophosphamide; lymphodepletion; Drug: Fludarabine; lymphodepletion; Biological: EB-CAR30-NK; CD30-targeted allogeneic CAR-NK cells; Biological: EB-CAR5-NK; CD5-targeted allogeneic CAR-NK cells; Biological: EB-CARMSLN-NK; Mesothelin-targeted allogeneic CAR-NK cells; Drug: Rimiducid (AP1903); ctivate the iCasp9 safety switch if clinically indicated
Experimental: 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.	Drug: Cyclophosphamide; lymphodepletion; Drug: Fludarabine; lymphodepletion; Biological: EB-CAR30-NK; CD30-targeted allogeneic CAR-NK cells; Biological: EB-CAR5-NK; CD5-targeted allogeneic CAR-NK cells; Biological: EB-CARMSLN-NK; Mesothelin-targeted allogeneic CAR-NK cells; Drug: Rimiducid (AP1903); ctivate the iCasp9 safety switch if clinically indicated
Experimental: 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.	Drug: Cyclophosphamide; lymphodepletion; Drug: Fludarabine; lymphodepletion; Biological: EB-CAR30-NK; CD30-targeted allogeneic CAR-NK cells; Biological: EB-CAR5-NK; CD5-targeted allogeneic CAR-NK cells; Biological: EB-CARMSLN-NK; Mesothelin-targeted allogeneic CAR-NK cells; Drug: Rimiducid (AP1903); ctivate the iCasp9 safety switch if clinically indicated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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	Proportion of participants with CR, PR, or stable disease	12 months

Collaborators and Investigators

• Sponsor: Beijing Biotech

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): April 17, 2028

Study Registration Dates

• First Submitted: May 14, 2026
• First Submitted That Met QC Criteria: May 14, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Mesothelin; Adoptive cell therapy; CAR-NK; Natural killer cells; CD30; Biomarker-guided; CD5; Solid tumor immunotherapy; Thymic epithelial tumor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Thoracic Neoplasms; Lymphatic Diseases; Neoplasms, Complex and Mixed; Thymus Neoplasms; Hemic and Lymphatic Diseases; Thymoma; Thymic epithelial tumor; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine; AP 1903 reagent
• Other Study ID Numbers: EB-CARNK-THYM-009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No