AstraZeneca showcases strength of haematology portfolio and pipeline at ASH 2024

First results from AMPLIFY trial will reinforce Calquence as leading second-generation BTK inhibitor in frontline chronic lymphocytic leukaemia with fixed-duration regimen Next generation cell therapy and T-cell engagers will demonstrate promising early results in multiple types of blood cancer New, long-term data for Voydeya as add-on to Ultomiris or Soliris will show low rate of breakthrough haemolysis events and sustained improvements in quality-of-life measures in PNH with extravascular haemolysis AstraZeneca advances its ambition to redefine cancer care with new data across its industry-leading and diverse pipeline in haematology at the 66 th American Society of Hematology (ASH) Annual Meeting and Exposition 7 to 10 December 2024. A total of 57 abstracts will feature 13 approved and potential new medicines from across AstraZeneca’s portfolio and pipeline in haematology, including from Alexion, its rare disease group, with data in key settings including chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), paroxysmal nocturnal haemoglobinuria (PNH) and other haematologic diseases. Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: “Our data at ASH from the AMPLIFY Phase III trial will demonstrate the efficacy and safety of our leading second-generation BTK inhibitor, Calquence, as a fixed-duration therapy in first-line CLL. In addition, new results for our novel T-cell engager, AZD0486, will reinforce its promising clinical profile in lymphomas, and data for our novel CAR T cell therapy, AZD0120, will highlight the potential of this therapy to transform treatment in multiple myeloma.” Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “Our ASH presentations will highlight the transformative impact of our medicines, including new analyses from the ALPHA Phase III trial reaffirming the safety and efficacy of our first-in-class Factor D inhibitor Voydeya as add-on to Ultomiris or Soliris for the subset of patients with PNH experiencing clinically significant extravascular haemolysis. Further, new insights from our robust pipeline will enhance the understanding of several rare haematologic and cardiovascular conditions, underscoring our commitment to innovation in rare disease.” Calquence combinations demonstrate significant benefits across CLL and MCL An oral presentation on interim results from the pivotal AMPLIFY Phase III trial will demonstrate the potential of fixed-duration Calquence in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy. 1 These results will be featured during the ASH Press Briefing on Sunday 8 December. An updated analysis from the pivotal ECHO Phase III trial will further highlight the use of Calquence in combination with bendamustine and rituximab as a first-line treatment option by demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL) as well as showing the benefit of Calquence across all patients including those with high-risk disease characteristics. 2 Results from ECHO were first presented as a late-breaking oral presentation at the European Hematology Association (EHA) 2024 Hybrid Congress in June. 3 Results will also be shared from the ChangE Phase III trial, evaluating Calquence compared with chlorambucil plus rituximab in first-line CLL in patients in China. 4 New data show promise of next generation T-cell engagers and chimeric antigen receptor T-cell (CAR T) therapy Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing the potential of this novel medicine as a new treatment option for B-cell malignancies. 5,6 Phase I results demonstrate high response rates, with a 96% overall response rate, 85% complete response rate and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above. 5 Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL). 6 Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule. 7 Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR rapid manufacturing process, will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM. 8 Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population. 8 An oral presentation will share preclinical data demonstrating the anti-tumour activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL. 9 Voydeya (danicopan) as add-on to Ultomiris (ravulizumab) or Soliris (eculizumab) demonstrates low rate of mild or moderate BTH events and improves quality of life measures in patients with PNH and clinically significant EVH Data will be presented detailing events of breakthrough haemolysis (BTH), a key indicator of intravascular haemolysis and PNH disease control, reported in the ALPHA trial evaluating Voydeya as add-on to Ultomiris or Soliris in patients with PNH experiencing clinically significant extravascular haemolysis (EVH) and separately in the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with Soliris . Data will show that 5/84 patients (6.0%) in the ALPHA trial and 19/80 patients (23.8%) in the PEGASUS trial experienced one or more BTH events. Moreover, most BTH events (6/7 or 85.7%) in the ALPHA trial were either mild or moderate, and all events were resolved without transfusion, dose modification or treatment withdrawal. 10 Separately, final long-term patient-reported outcomes from the ALPHA trial will demonstrate Voydeya as add-on to Ultomiris or Soliris resulted in sustained improvements in fatigue, quality of life and physical function for up to 72 weeks in the subset of patients with PNH who experience clinically significant EVH. 11 Advancing understanding of life-threatening rare diseases A US, retrospective chart review will provide real-world evidence showing haematologic and renal improvements in adults with atypical haemolytic uraemic syndrome (aHUS) who switched to Ultomiris after short-term use of Soliris , with early responses and continued improvements through one year of treatment with Ultomiris . 12 Additionally, two presentations on amyloid light chain (AL) amyloidosis will highlight unmet medical needs in this progressive, debilitating disease, reinforcing the importance of bringing forward novel therapies to improve cardiovascular outcomes and organ function. 13,14 Key presentations during the 66th ASH Annual Meeting and Exposition Lead Author Abstract Title Presentation details (PST) Calquence (acalabrutinib) Brown, JR et al. Fixed-Duration Acalabrutinib plus Venetoclax with or without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial Abstract #1009 Oral Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Frontline Targeted Therapy Combinations 9 December 2024 4:30 PM Qiu, L et al. Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open Label, Phase 3 Study Abstract #3251 Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II 8 December 2024 6:00 – 8:00 PM Dreyling, M et al. High-risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma Abstract #1626 Poster Session 623. Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I 7 December 2024 5:30 – 7:30 PM Simon, F et al. Efficacy and Safety of Acalabrutinib Treatment in Very Old (≥80y) and/or Frail Patients with Chronic Lymphocytic Leukemia (CLL) – Primary Endpoint Analysis of the Phase II CLL-Frail Trial Abstract #4618 Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III 9 December 2024 6:00 – 8:00 PM Swaminathan, M et al. Early Obinutuzumab Significantly Increases Bone Marrow Undetectable MRD (10 -4 sensitivity) (uMRD4) Rate when Combined with Acalabrutinib and Venetoclax in a Randomized Phase II Trial for Treatment Naïve CLL Abstract #1855 Poster Session 642: Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I 7 December 2024 5:30 – 7:30 PM Jerkeman, M et al. Acalabrutinib and Rituximab in Elderly Patients with Newly Diagnosed Mantle Cell Lymphoma Including a Matched Population-Based External Comparator- the Nordic Lymphoma Group NLG-MCL8 (ALTAMIRA) Phase II Trial Abstract #747 Oral Session 623: Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Updates on Drug Treatments for Mantle Cell Lymphoma, and CAR-T and Transplants for Indolent Lymphomas 9 December 2024 11:00 AM Christofyllakis, K et al. Toxicity of R-mini-CHOP with or without Acalabrutinib in Older Adults with Untreated DLBCL – An Interim Analysis of Serious Adverse Events in the ARCHED / GLA 2022-1 Randomized, Open-Label, Phase 3 Trial Abstract #4498 Poster Session 627: Aggressive Lymphomas: Pharmacologic Therapies: Poster III 9 December 2024 6:00 – 8:00 PM AZD0486 Gaballa, S et al. Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T–naive and CAR-T–exposed Patients Abstract #868 Oral Session 627: Aggressive Lymphomas: Pharmacologic Therapies: Novel Monotherapies or Novel Disease Indications 9 December 2024 3:30 PM Hou, J et al. Escalating Doses of AZD0486, a Novel CD19xCD3 T-cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma Abstract #341 Oral Session 623: Mantle Cell, Follicular, Waldenstrom’s and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Novel Treatment Strategies and New Data on Old Standards for Follicular Lymphoma 7 December 2024 5:00 PM Zhu, X et al. Exposure-Response analysis and Quantitative Systems Pharmacology modelling for an optimal dose selection of AZD0486 in follicular lymphoma patients Abstract #2794 Poster Session 605: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II 8 December 2024 6:00 – 8:00 PM AZD0120 Du, J et al. A phase I study of dual targeting BCMA and CD19 FasTCAR-T cells (GC012F) as first-line therapy for transplant-ineligible newly diagnosed multiple myeloma Abstract #2072 Poster Session 704: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I 7 December 2024 5:30 – 7:30 PM AZD5492 Lawrence, R et al. Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non-Hodgkin Lymphoma Indications Abstract #959 Oral Session 605: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma 9 December 2024 5:30 PM Voydeya (danicopan) Schrezenmeier, H Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from Danicopan and Pegcetacoplan Trials Abstract #2694 Poster Session 508: Bone Marrow Failure: Acquired: Poster II 8 December 2024 6:00 PM Piatek, C Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial Abstract #2692 Poster Session 508: Bone Marrow Failure: Acquired: Poster II 8 December 2024 6:00 PM Ultomiris (ravulizumab) and Soliris (eculizumab) Griffiths, E Real-World Drug Adherence, Persistence, and Healthcare Resource Utilization in Patients with Paroxysmal Nocturnal Hemoglobinuria in the USA: The ADVANTAGE Study Abstract #5074 Poster Session 905: Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies 9 December 2024 6:00 PM Chaturvedi, S Real-World Effectiveness of Ravulizumab Among Adults with Atypical Hemolytic Uremic Syndrome (aHUS) who Switched to Ravulizumab Within 3 Months of Eculizumab Treatment: A Physician Panel-Based Chart Review Study (aHUS IMPACT) Abstract #2613 Poster Session 330: Vascular Biology, Thrombosis, and Thrombotic Microangiopathies: Basic and Translational 8 December 2024 6:00 PM Iori, AP REACTION - Real Life Use of Ravulizumab in Italian PatiEnts with PAroxysmal NoCturnal Hemoglobinuria a MulTicenter ObservatIONal Retrospective and Prospective Cohort Study, Final Results Abstract #2464 Poster Session 101: Red Cells and Erythropoiesis, Excluding Iron 8 December 2024 6:00 PM PNH Wagner-Ballon, O High Proportion of PNH Type II Neutrophils, l.e Relative Percentage 3%, Is Associated with Thrombosis in Patients Displaying a PNH Clone >1%: Evidence from Analysis of the 5-Year French Nation-Wide Multicenter Observational Study Abstract #4080 Poster Session 508: Bone Marrow Failure: Acquired: Poster III 9 December 2024 6:00 PM HSCT-TMA Dandoy, C Survival Outcomes in Adult and Pediatric Patients Who Experienced Thrombotic Microangiopathy After Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis Abstract #7286 Online Publication Amyloidosis Laires, P Comparison Of Alternative Mayo Staging Classification Systems Used in Light-Chain Amyloidosis Abstract #6887 Online Publication Thompson, J Evaluation of Functional Cardiac Measures and Response to Treatment Initiation in Patients with Systemic Light-Chain (AL) Amyloidosis: Results from a Single Site Retrospective Study Abstract #4677 Poster Session 652: MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological 9 December 2024 6:00 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 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 . References Brown, J et al. Fixed-Duration Acalabrutinib plus Venetoclax with or without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial. Presented at ASH 2024. Abstract 1009. 2024. Dreyling, M et al. High-risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma. Presented at ASH 2024. Abstract 1626. 2024. Wang, M et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: Results from the Phase 3, Double-Blind, Placebo-Controlled ECHO Trial. Presented at EHA 2024. Abstract LBA3439. 2024 Qiu, L et al. Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open Label, Phase 3 Study. Presented at ASH 2024. Abstract 3251. 2024. Gaballa, S et al. Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T–naive and CAR-T–exposed Patients. Presented at ASH 2024. Abstract 868. 2024. Hou, J et al. Escalating Doses of AZD0486, a Novel CD19xCD3 T-cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma. Presented at ASH 2024. Abstract 341. 2024. Zhu, X et al. Exposure-Response analysis and Quantitative Systems Pharmacology modelling for an optimal dose selection of AZD0486 in follicular lymphoma patients. Presented at ASH 2024. Abstract 2794. 2024. Du, J et al. A phase I study of dual targeting BCMA and CD19 FasTCAR-T cells (GC012F) as first-line therapy for transplant-ineligible newly diagnosed multiple myeloma. Presented at ASH 2024. Abstract 2072. 2024. Lawrence, R et al. Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non-Hodgkin Lymphoma Indications. Presented at ASH 2024. Abstract 959. 2024. Schrezenmeier H, Mahdi M, Gasteyger C, et al. Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from Danicopan and Pegcetacoplan Trials. Presented at ASH 2024. Abstract 2694. 2024. Piatek C, Lee JW, Griffin M, et al. Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial. Presented at ASH 2024. Abstract 2692. 2024. Chaturvedi S, Wang Y, Ong M-L, et al. Real-World Effectiveness of Ravulizumab Among Adults with Atypical Hemolytic Uremic Syndrome (aHUS) who Switched to Ravulizumab Within 3 Months of Eculizumab Treatment: A Physician Panel-Based Chart Review Study (aHUS IMPACT). Presented at ASH 2024. Abstract 2613. 2024. Laires P, Thompson J, Catini J, et al. Comparison of Alternative Mayo Staging Classification Systems Used in Light-Chain Amyloidosis. Presented at ASH 2024. Abstract 6887. 2024. Thompson J, Catini J, Ouyang D, et al. Evaluation of Functional Cardiac Measures and Response to Treatment Initiation in Patients with Systemic Light-Chain (AL) Amyloidosis: Results from a Single Site Retrospective Study. Presented at ASH 2024. Abstract 4677. 2024. tags Oncology Corporate and financial AstraZeneca Websites This website is intended for people seeking information on AstraZeneca's worldwide business. Our country sites can be located in the AZ Network. 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