A Phase 1b, Open-label, Multi-center, Randomized Study Evaluating the Safety and Tolerability of AZD0120, an Autologous CD19/BCMA Targeting Chimeric Antigen Receptor T-cells, in Adults With Refractory Relapsing or Progressive Multiple Sclerosis

This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with Multiple Sclerosis.

开始日期2025-12-23

申办/合作机构

AstraZeneca PLC

NCT07250269

/ Recruiting临床1期

A Phase 1b Study of GC012F, a Chimeric Antigen Receptor T Cell Therapy Targeting CD19 and B-cell Maturation Antigen in Chinese Participants With Relapsed or Refractory AL Amyloidosis

This is a Phase 1b open-label, multicenter, non-randomized study of GC012F, a CD19/BCMA dual CAR T cell therapy, in adult participants with relapsed/refractory AL amyloidosis.

开始日期2025-10-29

申办/合作机构

亘喜生物科技（上海）有限公司

[+1]

NCT07086404

/ Not yet recruiting早期临床1期IIT

Early Exploratory Clinical Study of GC012F Injection in Refractory Idiopathic Inflammatory Myopathy

This is a single-arm, open-label, early exploratory clinical study to evaluate the safety and efficacy of GC012F Injection in subjects with refractory idiopathic inflammatory myopathy and to assess the pharmacokinetic and pharmacodynamic profiles.
This study consists of screening period, apheresis period, baseline period, lymphodepleting preconditioning period, pre-infusion evaluation period, CAR-T cell infusion period and follow-up period.
Eligible subjects will undergo apheresis and receive infusion following the manufacture of the CAR-T product. Subjects will receive lymphodepleting preconditioning before CAR-T cell infusion and will be assessed before infusion. If the criteria for cell infusion are met, CAR-T cell infusion will be performed and the infusion dose in the same group or subsequent treatment groups may be adjusted according to the safety and clinical response.
A total of 1 dose group will be set for CAR-T cell infusion dose in this study: 3 ? 10^5/kg. Approximately 12 subjects are planned to be enrolled. Subjects will be monitored for dose-limiting toxicity (DLT) within 28 days following the infusion of GC012F Injection. For the first 3 patients receiving infusions of GC012F, 3 additional patients will be included in this cohort if no more than 1/3 of the patients experience DLTs at a given dose level. If 2/3 or more DLTs occur at this dose level, a spare dose of 2.0 ? 10^5/kg or 1.0 ? 10^5/kg may be administered to subsequent subjects following discussion between the investigator and the partner. If no more than 1 out of the first 6 subjects experiences a DLT, 6 additional subjects will be enrolled. Once 2 subjects experience DLTs, the investigator and the partner will discuss and decide whether to use a spare dose group of 2.0?10^5/kg or 1.0?10^5/kg.
After the first 3 subjects have all completed the 28-day DLT observation period, the Safety Monitoring Committee (SMC) will conduct an assessment based on clinical safety and pharmacokinetic data (if available). Subsequently, the SMC may, depending on the safety profile and study progress, request an increased frequency of safety committee assessments and reviews. After completing the DLT observation period for all subjects in this dose group, all clinical study data collected during the DLT observation period for this dose group, especially safety data, will be assessed, and whether to add new subjects to this dose group and whether to explore a different dose group will be decided upon discussion between the investigator and the partner.
Following CAR-T cell infusion, subjects will be followed for safety, cell proliferation and survival, and efficacy until the subject withdraws from the study and refuses subsequent follow-up, or dies, or withdraws consent, or is lost to follow-up, whichever occurs first.

开始日期2025-09-15

申办/合作机构

阿斯利康全球研发（中国）有限公司

[+1]

100 项与 GC-012F 相关的临床结果

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100 项与 GC-012F 相关的转化医学

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100 项与 GC-012F 相关的专利（医药）

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项与 GC-012F 相关的文献（医药）

2025-11-01·Transplantation and Cellular Therapy

Review

作者: Maloney, David G ; Locke, Frederick L ; Shah, Nirav N ; Neelapu, Sattva S ; Ng, Eric ; Davila, Marco ; Vong, Judy ; Jacobson, Caron ; Miklos, David B ; Nikiforow, Sarah ; Welch, John ; Lin, Yi ; Frigault, Matthew J ; Maus, Marcela V

Chimeric antigen receptor T-cell (CAR T) therapies have demonstrated potential to provide long-term remission in incurable hematologic malignancies, and novel approaches for CAR T therapy continue to be developed for treating cancer and other indications. Acute class-effect toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, remain significant concerns despite their potential reversibility. Given the complexities of balancing safety and efficacy of CAR T therapies, the US Food and Drug Administration (FDA) recently published Guidance for Industry, which included suggested definitions for dose-limiting toxicities (DLTs) for clinical trials of emerging CAR T therapies. However, the DLT definitions in the guidance do not reflect what was used in the phase 1 and/or registrational studies for the approved CAR Ts; for example, these studies defined DLTs as treatment-related, included exceptions, and/or allowed for time to resolve the adverse event. Using DLT definitions from the guidance could have prematurely stopped the early-phase studies of the now approved CAR Ts. In 2023, while designing a first-in-human, phase 1 study of a logic-gated cell therapy, an expert panel of academic cell therapists collaborated with industry partners at A2 Biotherapeutics to assess the practical implications of the FDA guidance. This led the panel to draft the revised recommendations contained herein, which integrate the permissibility of reversible events during dose-escalation for trial sponsors, investigators, health authorities, and other parties who may be involved in future CAR T therapy trials. These expert recommendations balance the safety of patients in early-phase trials with the potential long-term therapeutic opportunities for patients with terminal malignancies.

2025-10-01·AMERICAN JOURNAL OF HEMATOLOGY

CD19 Directed CAR T Therapy for Transformed Follicular Lymphoma: A CIBMTR Analysis

Article

作者: Shadman, Mazyar ; Iqbal, Madiha ; Gopal, Ajay ; Aljurf, Mahmoud ; Turtle, Cameron ; Herrera, Alex F. ; Wirk, Baldeep ; Thiruvengadam, Swetha Kambhampati ; Beitinjaneh, Amer ; Patel, Jinalben ; Vaughn, John ; Metheny, Leland ; Epperla, Narendranath ; Hong, Sanghee ; Hertzberg, Mark ; Jain, Tania ; Ahn, Kwang Woo ; Hamadani, Mehdi ; Oliver, Carolina ; Lian, Qinghua ; Mohty, Razan ; Manjappa, Shivaprasad

ABSTRACT:

Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19‐directed chimeric antigen receptor T‐cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30–86) and median prior lines of therapy was 4 (range: 1–18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow‐up of 25 months (range: 1–72) from CAR T infusion, the 2‐year overall survival (OS) was 57% (95% CI: 53–60) and progression‐free survival (PFS) was 43% (95% CI: 40–47). The 2‐year cumulative incidences of relapse or progression (rel/prog) and non‐relapse mortality (NRM) were 47% (95% CI: 44–51) and 9% (95% CI: 7–11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell–associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.

2025-09-01·Transplantation and Cellular Therapy

Review

作者: Shafey, Mona ; Doble, Brett ; Lilley, Helen ; Dickinson, Olivia

The true costs of chimeric antigen receptor T-cell (CAR T) delivery (i.e., all costs except acquisition costs) remain uncertain, with little guidance available to guide accurate estimation. Providers therefore may face challenges in estimating the costs of establishing or expanding CAR T services, particularly if they have limited business expertise or CAR T experience. This risks over- or under-estimation of CAR T delivery costs, with potential for inadequate provider reimbursement, resource challenges, and restricted patient access. Accurate estimation of CAR T delivery costs is an essential component of ensuring value-based healthcare that achieves the best possible patient outcomes, while also ensuring that providers are adequately compensated for service delivery. The purpose of this paper is to demonstrate how value-based CAR T service delivery can be facilitated using an Excel-based micro-costing framework ("tool") to derive accurate and transparent cost estimates that consider the full patient pathway from initial assessment through to 100 days post CAR T infusion. Micro-costing can be used to support robust CAR T business case development and ensure all individual components of the treatment pathway have been accounted for. The tool's flexibility allows providers to model different future scenarios (e.g., changes in the case mix) and test the impact of resource changes (e.g., adjusting staff experience levels) to make informed resourcing decisions. This facilitates identification of opportunities for efficiencies, resource reallocation, and service improvements, and supports providers in delivering CAR T therapy to as many eligible patients as possible. A clear and detailed understanding of CAR T delivery costs can also support validation of reimbursement levels, such as CAR T tariffs, mitigating the risk of provider underpayment for services. The publicly available micro-costing tool is the first to support costing across the full CAR T treatment pathway from initial patient assessment to long-term follow-up. It has the potential to transform provider approaches to CAR T program development, reducing reliance on assumptive costs and uncertainty, and instead offering an evidence-driven approach. Overall, the tool supports value-based and sustainable CAR T therapy delivery, with the aim of ensuring adequate reimbursement for providers while facilitating patient access to this potentially life-saving therapy.

311

项与 GC-012F 相关的新闻（医药）

2025-12-04

·astrazeneca.com

AstraZeneca advances haematology and cell therapy ambition with largest-ever presence at ASH

AstraZeneca advances its ambition to redefine haematology care with new data from its diverse pipeline and portfolio at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, 6-9 December 2025. This year’s ASH congress will feature the Company’s largest presence to date, with 65 abstracts across eight approved and investigational medicines, including 15 oral presentations. Key presentations include: Phase I trial of surovatamig: Updated results at three-year follow up from the ongoing first-in-human trial of surovatamig,aCD19xCD3 T-cell engager, in relapsed/refractory (R/R) follicular lymphoma (FL) (Oral Abstract #1005). DURGA-1 Phase Ib/II study: Initial data for AZD0120 in patients with R/R multiple myeloma (MM). AZD0120 is an investigational BCMAxCD19 chimeric antigen receptor T-cell (CAR T) therapy(Oral Abstract #269). ECHO Phase III trial: Results after 50 months of follow up evaluating Calquence (acalabrutinib)plus bendamustine and rituximab in the first-line treatment of mantle cell lymphoma (MCL) (Oral Abstract #885). ALXN1210-TMA-314 Phase III trial: Additionalresults from the open-label trial evaluating Ultomiris (ravulizumab) in paediatric patients with haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) (Oral Abstract #1052). Anas Younes, Senior Vice President, Haematology R&D and Chief Medical Officer, AstraZeneca, said: “We are advancing a broad pipeline of investigational therapies with the potential to redefine patient care across multiple types of blood cancer. At ASH, we are sharing meaningful progress with early efficacy and safety data for AZD0120, our first cell therapy, in multiple myeloma, and for surovatamig, a novel T-cell engager, in B-cell malignancies.” Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “At ASH, we look forward to demonstrating how pioneering science can drive meaningful advances for people living with rare haematologic conditions. New data on Ultomiris, including Phase III results in paediatric patients with HSCT-TMA, will show clinically meaningful overall survival and improved outcomes, highlighting our ongoing pursuit to realise the full potential of our medicines and their impact on treating rare conditions.” Additional highlights include: SYRUS Phase I/II trial: Updated safety and efficacy data for surovatamig in adolescent and adult patients with R/R B-cell acute lymphoblastic leukaemia (Abstract #3345) Phase I trial of surovatamig: Initial efficacy and safety data for surovatamig in R/R diffuse large B-cell lymphoma (Abstract #5514) AZD0120: Follow-up data from two investigator-initiated trials (IIT) in China evaluating AZD0120 as a first-line therapy in high-risk, newly diagnosed MM (Oral Abstract #258). TrAVeRse Phase II trial: Preliminary results evaluating Calquence plus venetoclax and rituximab in treatment-naïve MCL patients (Oral Abstract #884). AMPLIFY Phase III trial: Exploratory analyses supporting the safety and efficacy profile of Calquence in first-line chronic lymphocytic leukaemia, with new subgroup data evaluating the impact of prognostic mutations on clinical outcomes (Poster Abstract #3898). ALPHA Phase III trial: Sub-analysis of results evaluating Voydeya (danicopan) as add-on to Ultomiris or Soliris (eculizumab) in adults with paroxysmal nocturnal haemoglobinuria (PNH) and clinically significant extravascular haemolysis, including in patients with advanced age (Oral Abstract #949). Ultomiris: Real-world evidence highlighting the impact of Ultomiris in certain patient subgroups across approved indications, including in pregnant patients (Poster Abstracts #6238 and #4458). Key presentations during the 67th ASH Annual Meeting and Exposition Lead Author Abstract Title Presentation Details (ET) Lead Author Awan, F et al. Abstract Title Budget Impact of Fixed Duration Acalabrutinib in Combination with Venetoclax in Previously Untreated Chronic Lymphocytic Leukemia Patients in the United States Presentation Details (ET) Abstract #2627 Poster Abstract Session Session 902. Health Services and Quality Improvement: Lymphoid Malignancies: Poster I 6 December 2025 5:30 PM – 7:30 PM Lead Author Cheah, C et al. Abstract Title Analysis of predictive factors for POD24 in patients with previously untreated mantle cell lymphoma receiving bendamustine-rituximab with or without acalabrutinib in the Phase 3 ECHO trial Presentation Details (ET) Abstract #3578 Poster Abstract Session Session 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II 7 December 2025 6:00 PM – 8:00 PM Lead Author Ghia, P et al. Abstract Title Impact of prognostic mutations on outcomes with fixed-duration acalabrutinib-venetoclax combinations versus chemoimmunotherapy: An exploratory analysis from AMPLIFY Presentation Details (ET) Abstract #3898 Poster Abstract Session Session 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II 7 December 2025 6:00 PM – 8:00 PM Lead Author Hawkes, E et al. Abstract Title Acalabrutinib plus venetoclax and rituximab in patients with treatment-naive (TN) mantle cell lymphoma (MCL): Results from the phase 2 TrAVeRse study Presentation Details (ET) Abstract #884 Oral Abstract Session Session 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Single Agent and Combination therapy for MCL 8 December 2025 3:00 PM – 03:15 PM Lead Author Hou, J-Z et al. Abstract Title Real-world incidence of treatment-emergent (TE) cardiovascular (CV) events among chronic lymphocytic (CLL)/small lymphocytic lymphoma (SLL) patients receiving acalabrutinib (acala) or zanubrutinib (zanu) monotherapy Presentation Details (ET) Abstract #4506 Poster Abstract Session Session 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster II 7 December 2025 6:00 PM – 8:00 PM Lead Author Seymour, JF et al. Abstract Title A post hoc safety analysis of fixed-duration acalabrutinib-venetoclax combinations vs chemoimmunotherapy: Results from the Phase 3 AMPLIFY trial Presentation Details (ET) Abstract #2118 Poster Abstract Session Session 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I 6 December 2025 5:30 PM – 7:30 PM Lead Author Wang, ML et al. Abstract Title Time to third-line treatment after bendamustine-rituximab with or without acalabrutinib in patients with previously untreated mantle cell lymphoma: Updated analysis of the phase 3 ECHO trial after 50 months of follow-up Presentation Details (ET) Abstract #885 Oral Abstract Session Session 623. Mantle Cell, Follicular, Waldenstrom's, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Single Agent and Combination therapy for MCL 8 December 2025 3:15 PM – 3:30 PM Ultomiris (ravulizumab) Ultomiris (ravulizumab) Schoettler, M et al. Ultomiris (ravulizumab) Outcomes in pediatric patients with HSCT-TMA treated with ravulizumab Ultomiris (ravulizumab) Abstract #1052 Oral Abstract Session Session 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Outcomes, toxicities and late effects 8 December 2025 4:45 PM – 05:00 PM Ultomiris (ravulizumab) Chaudhury, S et al. Ultomiris (ravulizumab) Organ dysfunction in pediatric patients with HSCT-TMA treated with ravulizumab Ultomiris (ravulizumab) Abstract #4266 Poster Abstract Session Session 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Poster II 7 December 2025 6:00 PM – 8:00 PM Ultomiris (ravulizumab) Sherrard, H et al. Ultomiris (ravulizumab) Safety of ravulizumab use in pregnancy: Insights from a global pharmacovigilance analysis Ultomiris (ravulizumab) Abstract #4458 Poster Abstract Session Session 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster II 7 December 2025 6:00 PM – 8:00 PM Ultomiris (ravulizumab) Gandhi, S et al. Ultomiris (ravulizumab) Real-world analysis of ravulizumab safety and effectiveness in advanced age patients with paroxysmal nocturnal hemoglobinuria: Insights from the international PNH registry Ultomiris (ravulizumab) Abstract #6238 Poster Abstract Session Session 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster III 8 December 2025 6:00 PM – 8:00 PM Fasenra (benralizumab) Fasenra (benralizumab) Klion et al. Fasenra (benralizumab) Efficacy and safety of benralizumab in patients with hypereosinophilic syndrome: Results from the Phase 3 natron study Fasenra (benralizumab) Abstract #79 Oral Abstract Session Session 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Expanding the Therapeutic and Prognostic Landscape in Myeloproliferative Neoplasms, Mastocytosis and Hypereosinophilic Syndrome 06 December, 2025 9:30 AM - 9:45 AM Fasenra (benralizumab) Klion et al. Fasenra (benralizumab) Patient perspectives on the burden of hypereosinophilic syndrome: Results from the Phase 3 natron interview sub-study Fasenra (benralizumab) Abstract #4465 Poster Presentation Session 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster II 07 December, 2025 6:00 PM - 8:00 PM Voydeya (danicopan) Voydeya (danicopan) Kulasekararaj, A et al. Voydeya (danicopan) Danicopan add-on therapy demonstrates positive efficacy and safety outcomes in advanced age adults with paroxysmal nocturnal hemoglobinuria and clinically significant extravascular hemolysis: A sub-analysis of the phase 3 ALPHA trial Voydeya (danicopan) Abstract #949 Oral Abstract Session Session 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Antithrombotic Roulette: Balancing Risk, Cost, and Care 8 December 2025 2:45 PM – 03:00 PM Surovatamig Surovatamig Aldoss, I et al. Surovatamig Safety and efficacy of surovatamig (AZD0486) in adolescent and adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL): Updated results from the Phase 1/2 SYRUS study Surovatamig Abstract #3345 Poster Abstract Session Session 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II 7 December 2025 6:00 PM – 8:00 PM Surovatamig Cheah, C et al. Surovatamig SOUNDTRACK-B: A Phase 2 single-arm study to evaluate the efficacy and safety of surovatamig (AZD0486) in relapsed or refractory B-cell Non-Hodgkin lymphoma Surovatamig Abstract #3747 (TiP) Poster Abstract Session Session 629. Aggressive Lymphomas, Immunotherapy including Bispecific Antibodies: Poster II 7 December 2025 6:00 PM – 8:00 PM Surovatamig Hou, JZ et al. Surovatamig Three-year follow-up of the Phase 1 first-in-human study investigating surovatamig, a novel CD19xCD3 T-cell engager, in patients with relapsed/refractory (R/R) follicular lymphoma (FL) Surovatamig Abstract #1005 Oral Abstract Session Session 623. Mantle Cell, Follicular, Waldenstrom's, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological - Follicular Lymphoma 8 December 2025 5:00 PM – 5:15 PM Surovatamig Kim, TM et al. Surovatamig Surovatamig (AZD0486), a CD19xCD3 T-cell engager (TCE), demonstrates high rate of minimal residual disease (MRD)-negative complete responses in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), including in patients who previously progressed on CD20 TCE and CD19 CAR T-cell therapies Surovatamig Abstract #5514 Poster Abstract Session Session 629. Aggressive Lymphomas, Immunotherapy including Bispecific Antibodies: Poster III 8 December 2025 6:00 PM – 8:00 PM AZD0120 AZD0120 Du, J et al. AZD0120 A dual targeting BCMA and CD19 FasTCAR-T (GC012F/AZD0120) as first-line therapy for newly diagnosed multiple myeloma AZD0120 Abstract #258 Oral Abstract Session Session 655. Multiple Myeloma: Cellular Therapies: Clinical Trial Advances in CAR T-Cell Therapy for Multiple Myeloma 6 December 2025 2:15 PM – 2:30 PM AZD0120 Richard, S et al. AZD0120 Safety and efficacy of AZD0120, a BCMA/CD19 dual-targeting CAR T-cell therapy, in relapsed/refractory multiple myeloma: Preliminary results from the DURGA-1 Phase 1b/2 study AZD0120 Abstract #269 Oral Abstract Session Session 704. Multiple Myeloma: Cellular Therapies: Clinical Trial Advances in CAR T-Cell Therapy for Multiple Myeloma 6 December 2025 3:00 PM – 3:15 PM AZD0120 Feng, J et al. AZD0120 One-year follow-up of CD19/BCMA dual-targeting FasTCAR-T GC012F (AZD0120) therapy in patients with refractory systemic lupus erythematosus AZD0120 Abstract #2384 Poster Abstract Session Session 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I 6 December 2025 5:30 PM – 7:30 PM AZD0120 Lentzsch, S et al. AZD0120 ALACRITY: A Phase 1b/2 Study of AZD0120 (BCMA/CD19 CAR-T cell therapy) in Participants with Relapsed or Refractory Light Chain Amyloidosis (AL) AZD0120 Abstract #8236 ePublication 3 November 2025 AZD4512 AZD4512 Han, H et al. AZD4512 AZD4512: A novel CD22-directed antibody-drug conjugate for the treatment of b-cell malignancies AZD4512 Abstract #3296 Poster Abstract Session Session 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II 7 December 2025 6:00 PM – 8:00 PM Notes AstraZeneca in haematology AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians. In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies. AstraZeneca in cell therapy AstraZeneca’s ambition is to realise the full potential of cell therapies. It is focused on empowering the immune system to attack cancers, reset the underlying drivers of immune-mediated diseases to return patients to health, and provide transformative solutions with curative potential for people living with rare diseases. To achieve this, the Company is building world-class cell therapy capabilities and advancing a broad pipeline of cell therapies, enabled by technologies including chimeric antigen receptor T-cells (CAR T), T-cell receptor therapies (TCR T) and CAR T regulatory (CAR Tregs) cells. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. Alexion Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. Oncology Corporate and financial

临床结果临床3期临床2期细胞疗法免疫疗法

2025-11-26

·空之客

【药海听涛】CAR-T和TCE决战紫禁之巅：B细胞清除药物临床数据全景图

近些年来，自身免疫疾病的热度毋庸置疑，其中B细胞清除机制更是烈火烹油。如果说2024年是TCE之年，2025年则是invivo CAR-T之年，MNC动辄豪掷数以十亿计的真金白银，誓要守护未来自免治疗的旗帜。记得去年笔者在基金内部讨论这个领域时，经常产生的疑惑在于“为什么CAR-T被Schett验证之后大家要一窝蜂去买TCE”；到了今年，这个疑惑演变成了“为什么一窝蜂买完了TCE又要回头去一窝蜂搞invivo CAR-T”……面对这种挠头的局面，笔者作为外行又不可能给出机制孰优孰劣的说辞，只能化简就繁，从各家能拿出的临床数据入手，看看CAR-T和TCE决战紫禁之巅到底打出个什么结果了？（须做说明的是，目前B细胞清除机制的这些药物几乎全都在早期临床、甚至IIT，跨试验对比数据至多只有示意性意义；此外，虽然有少数管线尝试了多种自身免疫疾病，但本文只重点选取了针对交集最多的SLE适应症结果进行对比分析。） 1 自体CAR-T 上帝说CAR-T能治自身免疫疾病，于是便有了George Schett大神。在George教授几乎是以一己之力奠定B细胞清除机制在自免的天胡开局之后，三四年时间过去了，向身后看去似乎依然一骑绝尘，跟进的CD19 CAR-T们非但难以重现炸裂的有效性、甚至连细胞治疗惯有的CRS和ICANS风险都难以回避，只能寄希望于几家中国公司的双靶点CAR-T排列组合。 1.1 Dr. Schett：MB-CART19.1（CD19 CAR-T）作为开山祖师爷，Schett教授主导的CASTLE系列试验，无疑给全行业立下了“开局即巅峰”的丰碑。在10例SLE患者中有9例达到Doris缓解，B细胞清除中位时间达到120天，CAR-T峰值中位数达到120 cells/uL，所有患者均实现免疫抑制剂停用，且没有三级以上CRS或任何ICANS。目前工业界的CAR-T或其他机制，都还没有真正超越这样漂亮的临床结果。 1.2 Cabaletta：CABA-201（CD19 CAR-T） Cabaletta应该是最早正经用CAR-T冲击自免疾病的Biotech，一口气推了Myositis、SLE、SSc、gMG、MS、PV等一系列适应症。在初步公布的SLE结果中，4例接受治疗半年以上患者中有3例实现Doris缓解，B细胞清除中位时间超过50天，此外在SSc试验中还验证了淋巴结内深度的B细胞清除；所有患者中，CRS仅有1级，但有1例LN患者发生了4级ICANS和4级全血细胞减少。 1.3 药明巨诺：Relma-cel（CD19 CAR-T）作为国产CAR-T的先驱者之一，药明巨诺在自免方向的尝试较早。在最初8例患者中实现了5例Doris缓解，B细胞清除维持至少5周时间，CAR-T峰值中位数93 cells/uL、CAR基因峰值中位数6.5E4 copies/ugDNA；目前所有CRS均为1级，但有1例患者出现2级ICANS。 1.4 亘喜/AZ：GC-012F（CD19xBCMA FasT CAR-T）亘喜是最早被MNC整体收购的细胞治疗公司（甚至一度也是整个中国Biotech被收购的标杆），AZ买了自然就是看重冲击自免的预期。在IIT的10例患者中有7例实现Doris缓解，B细胞清除中位时间84天，CAR基因峰值2E4 copies/ugDNA；CRS全部为1/2级，没有ICANS，不过3级以上血液毒性发生率够高的。考虑到该试验较重的基线，应该说药效是比较亮眼的，不过这次ACR与半年前EULAR好像也没多少新东西，年初就启动的大手笔150例注册临床才更值得期待。 1.5 西比曼：C-CAR-168（CD20xBCMA CAR-T）西比曼是另一家早早就抱上J&J大腿的中国公司，不过这个双靶CAR-T似乎并不在合作范围内。目前已治疗超过半年的4例患者中有2例实现Doris缓解，B细胞清除时间约2月，CAR基因峰值约1E5 copies/ugDNA；CRS均为1/2级，没有ICANS。 1.6 Autolus：Obe-cel（CD20xBCMA CAR-T） Obe-cel作为已获批血液瘤的品种也继续向自免延伸，在治疗半年以上的6例患者中有5例实现Doris缓解，B细胞清除中位时间居然高达6月，CAR基因峰值9E4 copies/ugDNA；CRS全部为1级，没有ICANS。这应该是目前注册临床中最接近Schett的数据。 1.7 雅科生物：CD19xBCMA CAR-T 这个似乎连代号都不容易查到的管线，不声不响摸出了一篇Nat Med。15例患者中有12例实现了Doris缓解，B细胞清除时间约2月、特别是有3例患者进行了PBMC和BMMC的测序证实了深度的B细胞清除，CAR基因峰值100-500 copies/uL（分别对应CD19和BCMA）；所有CRS均为1级，没有ICANS。不过雅科似乎近年在一堆子刊上发了不少文章，注册临床的声音却仙踪难觅。 2 异体CAR-T 犹记得小甜甜invivo CAR-T现身之前，牛夫人UCAR-T才是下一代细胞治疗的希望之星，资本在寒冬中又兴趣寥寥，让这个方向的发展大打折扣。即使近期涌现出北恒和邦耀等亮眼的中国IIT数据，但UCAR-T原本最重要的成本优势，在invivo面前似乎可能遭遇降维打击，好像临床表现显得依旧意兴阑珊。 2.1 北恒生物：CTA-313（CD19xBCMA UCAR-T）北恒毫无争议是今年ACR上最靓的仔，数据漂亮不说，而且展现形式从容大方，全不似一个小公司的IIT。在14例患者中有6例实现Doris缓解、不过可惜的是高剂量组只有1/4反而偏低，B细胞清除中位时间超过6周、且重建后naive细胞占绝大多数，CAR基因峰值1E6 copies/ugDNA；仅5例发生CRS且全部为1级，高剂量组反而完全没有CRS。 2.2 邦耀生物：BRL-303（CD19 UCAR-T）虽然只有4例数据，邦耀也可圈可点，毕竟4例全都Doris缓解实属不易，B细胞清除也达到1月，CAR峰值1E4 copies/ugDNA、CAR-T峰值75 cells/uL；CRS只有1级，没有ICANS。 2.3 Fate：FT-819（iPSC来源CD19 UCAR-T）邪修版本的Fate，基本上算是废特了。试图减少清淋、甚至不清淋，然而无论是SLEDAI-2K评分、还是B细胞清除，都并不理想。 2.4 Cartesian：Decartes-08（mRNA转染BCMA UCAR-T）另一大邪修Cartesian在笛卡尔的名号加持下，居然还算有模有样。在相对较轻的基线背景下，治疗超过3月的3例患者中有2例实现Doris缓解，也没有3级以上不良反应。 3 体内CAR-T 火归火，invivo CAR-T玩家们普遍刚进入IIT，真正能拿出来临床数据者寥寥无几。而在为数不多的这些数据中，似乎带来的更多不是星辰大海的信心、而是满脸懵逼的困惑…… 3.1 虹信生物：HN-2301（tLNP CD19 invivo CAR-T）我当然理解早期探索的珍贵，但面对这篇顶着中国invivo CAR-T领跑者之名高居NEJM上的文章，依然表达十分的不李姐：论转染效率，不同患者之间异质性太大不稳定；论B细胞清除，也完全谈不上干净；论SLEDAI-2K评分降低，不说Doris缓解吧，基本是聊胜于无，而且是在多个患者基线就已经很低的情况下……只能说我们应该向前瞻的研究者和伟大的受试者们致敬。 3.2 EsoBiotec：ESO-T01（LVV BCMA invivo CAR-T） Eso是最早发表IIT结果（虽然是治疗MM）的invivo CAR-T公司之一，据称也因此率先被AZ纳入麾下。不过先驱一定带着更多的疑点，例如不同患者之间针对T细胞亚群转染效率的巨大异质性，CAR-T数量峰值偏低，以及瘆人的3级CRS和ICANS，特别是输注后的高热、低血压血氧、以至意识模糊（还记得会上听梅恒主任讲到几个医生被迫4小时轮班盯守的惊心动魄），都还值得持续关注。 4 TCE 去年全球各大药企们一窝蜂往TCE上砸钱，豪掷近百亿美元几乎到了“应买尽买”的程度，然而转眼一年多过去，好像连个水漂都没见着，尤其是被下了重注的那几个分子，既无IIT结果公布、又无自免的注册临床进展。至于已经浮出水面的这些临床结果，与一众CAR-T相比还是略显单薄，至少与当初MNC的热情似乎极不相称。 4.1 天劢源和：A-319（CD19xCD3双抗）天劢源和的IIT数据，在TCE里算是最亮眼：治疗九个月以上的10例患者中有4例实现Doris缓解，B细胞清除至少6周（虽然给药就持续了4周）；没有3级以上CRS或ICANS，但有1例因不良反应而脱落。它的问题不在于数据不好，而在于这样的数据早在去年ACR就有雏形（6例），且注册临床迟迟不见下文，生生把优等生搁在半路上了。 4.2 惠和生物：CC-312（CD19xCD28xCD3三抗）增加CD28第二信号无疑是个勇敢的举措，然而惠和这个分子似乎并没有达到设计的初衷。低剂量5ug组B细胞清除都不干净，高剂量10ug组也做不到SLEDAI-2K归零，只能说是有药效、但不多。 4.3 Roche：Mosunetuzumab（CD20xCD3双抗）罗氏旗下已经获批的Mosunetuzumab，在自免的早期尝试也并不算成功。priming dose剂量几乎没什么效果自不必说，15/45mg两个目标剂量虽然看到一定的B细胞清除，但爬到60mg似乎清除得反而不干净了，SLEDAI-2K评分的下降也只是聊胜于无。 5 其他抛开CAR-T与TCE之争，也有超出三界外、不在五行中的玩家。 5.1 宜明昂科：IMM-0306（CD47xCD20双抗） CD47“钉子户”宜明昂科如今也算找到了出口，B细胞清除持续12周相当亮眼，但15例患者中无一实现Doris缓解还是有点无奈。 5.2 恩瑞恺诺：KN-5501（CD19 UCAR-NK）最开始看到恩瑞恺诺这个临床结果是非常惊艳的，18例患者中有13例实现Doris缓解，B细胞清除时间1月；只有1级CRS，没有ICANS。然而，经大佬提醒，似乎作为一个通用细胞治疗，它需要的donor数量有点略多了，加之恩瑞恺诺的IND拖了快两年才于近期获批，多少会引发一些猜想。完整数据以及所有看过的文献都放在知识星球了，看官大佬们欢迎支持取用~

细胞疗法免疫疗法ASH会议

2025-11-24

·百度百家

临床招募｜评估GC012F在自身免疫性疾病患者中的安全性和有效性的临床研究

最近，博医同行从社群和社交媒体上看到很多自身免疫性疾病的病友在经过CAR-T细胞免疫治疗后症状明显缓解，还有的病友已经逐渐停药。这让不少自免病友看到了新的曙光，也有越来越多的病友开始关注CAR-T项目进展。为帮大家更快地找到合适的新药机会，行仔特意整理了部分正在进行中的 CAR-T 相关临床试验项目，各位病友可扫码联系小助手咨询全部自免临床招募项目与详细入排标准。项目名称评估GC012F在自身免疫性疾病患者中的安全性和有效性的临床研究主要研究者张亚晶北京高博博仁医院主要入选标准年龄18-70岁，性别不限；筛选期或前6个月有活动性肌炎证据（肌肉活检/MRI），至少一种MSA/MAA阳性（如抗Jo-1、MDA-5）；中重度IIM（MMT<142），伴2项以上活动指标（如PhGA≥2cm、肌酶≥1.5×ULN）；活动性肌病证据（如CK≥4×ULN，或MRI/肌电图示炎症），经糖皮质激素+至少2种免疫抑制剂/生物制剂疗效不佳或不耐受；器官功能良好（如血红蛋白≥80g/L，肌酐清除率≥60mL/min），无严重肌肉萎缩或不受控肌外损害；同意避孕措施（至少2年或CAR-T细胞消失）。如您想进一步了解项目详情，请与项目联系人王娜15117940941或博医同行小助手联系。编辑 | 行仔排版 | 笑笑审核｜方玥立、贾冬雪

100 项与 GC-012F 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
免疫球蛋白轻链淀粉样变性	临床2期	美国	Alexion Pharmaceuticals, Inc.	2025-08-18
免疫球蛋白轻链淀粉样变性	临床2期	加拿大	Alexion Pharmaceuticals, Inc.	2025-08-18
免疫球蛋白轻链淀粉样变性	临床2期	英国	Alexion Pharmaceuticals, Inc.	2025-08-18
系统性红斑狼疮	临床2期	中国	亘喜生物科技（上海）有限公司	2024-08-15
难治性多发性骨髓瘤	临床2期	美国	AstraZeneca PLC	2023-07-20
复发性多发性骨髓瘤	临床2期	美国	AstraZeneca PLC	2023-07-20
多发性骨髓瘤	临床2期	中国	亘喜生物科技（上海）有限公司	2021-06-28
浆细胞白血病	临床2期	中国	亘喜生物科技（上海）有限公司	2021-06-28
原发性进行性多发性硬化	临床1期	美国	AstraZeneca PLC	2025-12-23
特发性炎症性肌病	临床1期	-	亘喜生物科技（上海）有限公司	2025-08-18

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05858684 (ACR2025)	临床1期	系统性红斑狼疮	10	GC012F (AZD0120)	鹽選製網鑰廠鹽壓襯積(艱鬱簾簾鑰糧願簾壓鏇) = Six patients experienced grade 1 CRS, and one patient experienced grade 2 CRS. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) or grade ≥3 CRS were reported. Other common AEs included hematologic abnormalities, hypogammaglobulinemia, and infections. No fatal adverse events occurred. 憲網廠網窪憲簾觸淵鬱 (糧繭廠蓋淵窪獵遞製夢 ) 更多	积极	2025-10-24
NCT05846347 (PS2146, EHA2025)	临床1期	系统性红斑狼疮 CD19 \| BCMA	15	GC012F	獵壓獵壓艱夢製簾鏇鏇(鹹齋蓋遞鹹選遞願膚餘) = 遞淵顧衊獵積鹹選鏇觸構廠簾鏇艱鏇製鹽鏇憲 (襯餘積遞構簾餘窪淵獵 ) 更多	积极	2025-05-14
NCT05840107 (PS1731, EHA2025)	临床1期	多发性骨髓瘤一线	9	GC012F/AZD0120 1.5x10^5/kg	壓醖製構窪獵鹽壓艱醖(構觸網餘選糧獵獵淵積) = 遞範夢願糧積繭網製築繭齋窪網鏇網廠顧夢選 (積獵齋蓋夢齋願餘餘壓 ) 更多	积极	2025-05-14
NCT05840107 (PS1731, EHA2025)	临床1期	多发性骨髓瘤一线	9	GC012F/AZD0120 3x10^5/kg	壓醖製構窪獵鹽壓艱醖(構觸網餘選糧獵獵淵積) = 夢襯鏇膚壓鬱製齋糧繭繭齋窪網鏇網廠顧夢選 (積獵齋蓋夢齋願餘餘壓 ) 更多	积极	2025-05-14
NCT04935580 (PS1711, EHA2025)	临床1期	多发性骨髓瘤一线 R-ISS stage II or III \| del (17p) \| t (4;14) ... 更多	22	GC012F/AZD0120 1x10^5/kg	獵膚餘築網衊範簾襯鏇(衊鑰鹽築選壓廠蓋衊艱) = 淵鏇鏇鑰積淵廠觸網鑰鏇鹹襯遞廠壓鹹繭衊繭 (構廠觸鏇鏇遞窪餘廠獵 ) 更多	积极	2025-05-14
NCT04935580 (PS1711, EHA2025)	临床1期		22	GC012F/AZD0120 2x10^5/kg	獵膚餘築網衊範簾襯鏇(衊鑰鹽築選壓廠蓋衊艱) = 壓襯繭鏇繭襯積積製鬱鏇鹹襯遞廠壓鹹繭衊繭 (構廠觸鏇鏇遞窪餘廠獵 ) 更多	积极	2025-05-14
NCT05840107 (ASH2024)	临床1期	多发性骨髓瘤一线	9	AZD0120+地塞米松+硼替佐米+来那度胺	製簾糧憲選憲願齋憲壓(選鑰網構繭齋鹽願築齋) = 願醖繭齋鹽壓積遞積齋廠築餘積願遞鹹鬱觸齋 (糧獵簾窪夢選淵窪壓選 ) 更多	积极	2024-12-07
NCT04935580 (EHA2024) 人工标引	临床1期	多发性骨髓瘤一线 CD19 ... 更多	22	GC012F CAR-T therapyGC012F10^5/kg	鏇簾夢廠壓鹹夢顧淵糧(鑰壓窪膚夢膚積餘襯淵) = 願觸窪觸網鏇膚鹹繭餘衊繭齋遞鑰襯廠鬱製糧 (憲壓襯壓窪積糧製構簾 ) 更多	积极	2024-05-14
ChiCTR2100047061 (EHA2024) 人工标引	早期临床1期	弥漫性大B细胞淋巴瘤	12	GC012F	鹹鏇願鬱鏇築壓觸製觸(獵網夢鬱廠製壓繭鬱衊) = included lymphocytopenia(11/12), neutropenia (11/12), leukopenia (10/12), and thrombocytopenia (3/12) 醖夢鹽鑰鏇淵艱壓簾餘 (蓋壓簾夢醖夢選鏇積鏇 )	积极	2024-05-14
NCT04935580 (ASH2023) 人工标引	临床1/2期	多发性骨髓瘤一线	22	GC012F	淵鏇醖鹹觸憲窪願糧觸(網艱獵積壓鹹窪製糧繭) = 壓鬱壓襯淵餘構餘夢製淵齋繭繭壓餘膚網蓋鏇 (淵齋願簾鬱網憲衊衊繭 ) 更多	积极	2023-12-11
NCT04935580 (IMS2023) 人工标引	临床1期	多发性骨髓瘤一线	19	GC012F	糧衊廠衊鑰窪遞衊築網(鑰遞蓋顧繭範繭鹹鑰齋) = 網積選窪糧簾蓋淵餘觸選構觸廠顧鏇顧願壓衊 (艱夢窪廠網顧糧蓋鹽廠 ) 更多	积极	2023-09-27
ChiCTR2100047061 (EHA2023)	早期临床1期	难治性B细胞淋巴瘤 CD19 \| BCMA	9	GC012F	廠顧淵顧鹽糧醖淵蓋齋(範夢夢鏇鏇積繭遞願膚) = 鹽觸餘廠餘網膚憲衊顧膚鏇艱窪範鹽遞觸構網 (遞築蓋廠衊鹹鹽網艱鹽 ) 更多	-	2023-06-08