Abstract Background and Significance Severe Aplastic Anemia (SAA) is a bone marrow failure disorder mediated by abnormally activated T-lymphocytes that lead to hematopoietic stem cell destruction. The standard of care for patients ineligible for or without a matched sibling donor for hematopoietic stem cell transplantation (HSCT) is immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), cyclosporine (CsA), and a TPO-receptor agonist (TPO-RA). However, a substantial number of patients are refractory to or relapse after initial IST, leaving them with limited therapeutic options and a poor prognosis. CD7 is a transmembrane glycoprotein highly expressed on T-cells and NK cells, which are central to the pathophysiology of SAA. CTD402 is a novel, allogeneic (“universal”) chimeric antigen receptor (CAR) T-cell therapy targeting CD7. Derived from healthy donors, CTD402, is a CD7 targeted “off-the-shelf” universal CAR-T product with T cell receptor and human leukocyte antigen class II knockout, and improved resistance to host immune rejection achieved by arming the cells with proprietary ANSWERTM inhibitory ligands. Preclinical studies demonstrated potent in vitro cytotoxicity and in vivo anti-tumor activity. Furthermore, this universal CD7 CAR T platform has shown effective T-lymphocyte depletion in patients with hematological malignancies. This study aims to translate this mechanism to SAA, where targeted T-cell depletion may eliminate pathogenic immune cells and allow for the restoration of normal hematopoiesis. ClinicalTrials.gov registration: NCT06622694.Study Design and Methods This is a phase I, single-arm, open-label, “3+3” dose-escalation and dose-expansion study conducted at a single center in China. The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of RD13-02 in patients with relapsed/refractory SAA. Approximately 15 patients will be enrolled Study Population & Key Criteria The study will enroll adults aged 18 to 75 years with a confirmed diagnosis of SAA who are refractory to or have relapsed at least 6 months after a standard course of IST containing ATG/ALG and a TPO-RA. Key exclusion criteria include pancytopenia from other causes (e.g., hypoplastic MDS), prior allogeneic HSCT or CAR T-cell therapy, significant cardiovascular, hepatic or renal dysfunction, and active, uncontrolled infections. Study Treatment Eligible patients will receive a standard lymphodepletion (sLD) regimen of fludarabine (25 mg/m²/day) and cyclophosphamide (500 mg/m²/day) for 3 days. This is followed by a single intravenous infusion of CTD402 cells. The dose-escalation phase will evaluate three dose levels (DL): DL1: 0.3×10⁸ CAR+ T cells；DL2: 0.5×10⁸ CAR+ T cells；DL3: 0.7×10⁸ CAR+ T cells. Endpoints The primary endpoint is to assess the safety and tolerability of RD13-02 and determine the maximum tolerated dose (MTD). Safety will be evaluated by the incidence of dose-limiting toxicities (DLTs), serious adverse events (SAEs), and other treatment-emergent adverse events (TEAEs). Key secondary endpoints include the overall hematologic response rate (ORR) at 3 and 6 months, duration of response, and the PK profile of RD13-02. Exploratory endpoints include the analysis of biomarkers related to immune reconstitution and disease activity. The study is currently recruiting patients.
Zhang et al. (Mon,) studied this question.
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