Qihan Biotech Initiates Phase I/IIa Trial of Off-the-Shelf CAR-T Therapy for Refractory Lupus
核心洞察
Qihan Biotech has initiated dosing in a Phase I/IIa clinical trial of QT-019B (搜索), an allogeneic CAR-T therapy for refractory systemic lupus erythematosus, with FDA Fast Track Designation for SLE-ITP.
Clinical data from investigator-initiated trials in 20 patients with multiple autoimmune diseases showed QT-019B (搜索) was well tolerated with no events exceeding Grade 1 cytokine release syndrome.
The therapy demonstrated clinical benefit across severe autoimmune conditions, including 5 complete responses in 6 SLE-ITP patients and 4 complete responses in 5 APS-associated ITP patients.
Qihan Biotech has initiated dosing in a Phase I/IIa clinical trial of QT-019B (搜索), an off-the-shelf allogeneic CAR-T therapy for the treatment of refractory systemic lupus erythematosus (rSLE). The study is being conducted under a US FDA IND and has received Fast Track Designation for SLE-associated immune thrombocytopenia (SLE-ITP), while also obtaining IND approval from the Chinese Center for Drug Evaluation.
Encouraging Clinical Results Across Multiple Autoimmune Diseases
Clinical data presented at the American Society of Hematology Annual Meeting demonstrated promising results from investigator-initiated trials involving 20 patients with multiple autoimmune diseases. Treatment with QT-019B (搜索) was generally well tolerated, with no events exceeding Grade 1 cytokine release syndrome and no reported immune effector cell-associated neurotoxicity syndrome or serious infections.
Across multiple severe autoimmune indications, QT-019B (搜索) demonstrated clinical benefit in patients dosed at therapeutically relevant levels (n=19). The efficacy results included:
- SLE-ITP (n=6): 5 complete responses with normalized platelet counts and 1 partial response
- APS-associated ITP (n=5): 4 complete responses with normalized platelet counts
- Autoimmune hemolytic anemia (n=3): 2 complete responses with normalized hemoglobin
- SLE (n=2): 1 DORIS remission and 1 SRI-4 response at Month 2
- Neurological autoimmune diseases (n=3): 2 EDSS stabilization cases
Advanced Engineering Platform Addresses Key Barriers
QT-019B (搜索) represents Qihan Biotech's first-generation allogeneic CAR-T therapy engineered using the company's immune-privileged platform. The therapy incorporates multiplex gene edits to enhance expansion, persistence, and resistance to immune rejection. Derived from healthy donor leukapheresis products, QT-019B is engineered to stably express two distinct chimeric antigen receptors targeting CD19 (搜索) and BCMA (搜索), enabling simultaneous recognition and elimination of cells expressing either antigen.
To reduce the risk of graft-versus-host disease, the T cell receptor is knocked out through gene-editing. Additionally, multiplex gene-editing strategies are used to confer hypoimmunity, reducing recognition and clearance by patients' endogenous T and NK cells.
"Autologous therapies have shown what cell therapy can achieve, but they are not scalable for autoimmune disease," said Luhan Yang, Ph.D., Chief Executive Officer of Qihan Biotech. "Our data show a different path. Our first-generation program demonstrates strong safety, robust in vivo expansion, meaningful efficacy, and evidence of immune reset."
Robust Pharmacokinetic and Pharmacodynamic Profile
The clinical data revealed robust expansion of allogeneic CAR-T cells in 17 of 19 patients treated at therapeutic dose levels. Deep and sustained depletion of pathogenic autoantibodies was observed, consistent with the intended immune-reset mechanism. In multiple sclerosis patients, early cerebrospinal fluid analyses showed rapid and durable clearance of oligoclonal bands and kappa free light chains.
Addressing Unmet Medical Need
"Refractory systemic lupus erythematosus represents a substantial unmet medical need and urgently calls for innovative therapeutic approaches," said Mengtao Li, M.D., Director at Peking Union Medical College Hospital and principal investigator of the study. "While autologous CAR-T therapy has enabled immune reset and long-term remission in some patients with SLE, challenges such as limited accessibility remain."
Phase I/IIa Trial Design
The QT-019B (搜索)-001CN trial is an open-label, single-arm, multicenter clinical study conducted in patients with rSLE. The protocol includes dose-escalation and dose-expansion stages, designed to evaluate the safety, tolerability, and efficacy of QT-019B in patients with rSLE, obtain pharmacokinetic and pharmacodynamic data, and determine the recommended dose for pivotal clinical studies.
Yang noted that QT-019B (搜索) has already been evaluated in investigator-initiated clinical trials involving more than 20 patients with autoimmune diseases, with encouraging results supporting the therapy's potential as an innovative and more accessible treatment option for patients with refractory systemic lupus erythematosus.