- Trial meets the primary endpoint of durable complete response
- Majority of patients who had a complete response had no evidence of any remaining detectable cancer cells
- Phase III clinical trial results served as basis for recent US FDA regulatory submission
CAMBRIDGE, 04-Jun-2018 — /EuropaWire/ — AstraZeneca and MedImmune, its global biologics research and development arm, today presented results from the Phase III (‘1053’) clinical trial that evaluated moxetumomab pasudotox in 80 patients with relapsed or refractory hairy cell leukaemia (HCL) who had received at least two prior lines of therapy.1
Moxetumomab pasudotox, an investigational anti-CD22 recombinant immunotoxin, showed a 75% objective response (OR) rate, a 41% complete response (CR) rate, and a 30% durable CR rate (primary endpoint). The majority of patients with a complete response had a durable response (73%; 24/33) and achieved a negative minimal residual disease (MRD) status (82%; 27/33). Findings from this pivotal trial were presented for the first time during an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA (Abstract #7004).
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “Moxetumomab pasudotox is an investigational, first-in-class immunotoxin which we believe has the potential to advance outcomes for patients with relapsed or refractory hairy cell leukaemia, a condition with a high unmet need. It is also the first agent to be submitted for regulatory review from our Antibody Drug Conjugates platform, and as such demonstrates our commitment to developing novel treatments for blood cancer.”
Robert J. Kreitman, MD, Senior Investigator, Head of Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, said: “Hairy cell leukaemia is a rare, chronic blood cancer with no established standard of care for patients with relapsed or refractory disease following purine nucleoside analogue therapy. With very few treatments available, there remains significant unmet medical need for people with relapsed or refractory disease. The response rates observed in this trial, and elimination of the residual leukaemia cells that cause relapse in some patients, highlight the potential impact this potential new medicine could have on patients and the management of this disease.”
Summary of key results from the Phase III ‘1053’ single arm, multicentre clinical trial in 80 patients with relapsed or refractory HCL (16.7 months median follow-up), as determined by a blinded independent central review:
Endpoint | Moxetumomab pasudotox |
OR rate | 75% (60/80) |
CR rate | 41% (33/80) |
Durable CR rate | 30% (24/80) |
Haematologic remission* (blood count normalisation, HR) rate | 80% (64/80) |
MRD negative status (CR rate with immunohistochemistry MRD negativity) | 82% (27/33) |
*Haematologic remission (HR) is defined by: neutrophils > 1.5 x 109 /L, platelets > 100 x 109 /L, haemoglobin > 11 g/dL, no transfusions / growth factors > 4 weeks
The primary endpoint of the trial was durable CR, which is defined as CR with HR for >180 days. The median time to HR was 1 month. MRD refers to the small amounts of cancer cells that may remain after treatment.2 A high rate of negative MRD after therapy may further improve outcomes.3 The median duration of OR and median progression-free survival were not reached.
The most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral oedema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropaenia deemed treatment-related. Three patient deaths occurred, none of which were determined to be treatment-related. Treatment-related AEs leading to discontinuation were haemolytic uraemic syndrome (HUS; 4 [5%]), capillary leak syndrome (CLS; 2 [3%]), and increased blood creatinine (2 [3%]). Seven patients (9%) had CLS and seven (9%) had HUS; this includes four (5%) patients who had both CLS and HUS. CLS and HUS were manageable and reversible.
In April 2018, AstraZeneca announced that the US Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for moxetumomab pasudotox for the treatment of adult patients with HCL who have received at least two prior lines of therapy. The BLA is based on results from the Phase III ‘1053’ clinical trial. The FDA has granted Priority Review status with a Prescription Drug User Fee Act action date set for the third quarter of 2018.
NOTES TO EDITORS
About Moxetumomab Pasudotox
Moxetumomab pasudotox (formerly CAT-8015 or HA22) is an investigational anti-CD22 recombinant immunotoxin and a potential new medicine with the opportunity to be a first-in-class treatment in the US for patients with relapsed or refractory hairy cell leukaemia (HCL) who have received at least two prior lines of therapy. Immunotoxins are a class of anticancer agents that combine the selectivity of antibodies to target drug delivery and the potency of toxins to kill target cancer cells.4Moxetumomab pasudotox is composed of a binding portion of an anti-CD22 antibody fused to a toxin. CD22 is a B-lymphocyte restricted transmembrane protein with a higher receptor density in HCL cells relative to normal B cells, making it an attractive therapeutic target for the treatment of this cancer.5 After binding to CD22, the molecule is internalised, processed and releases its modified protein toxin that inhibits protein synthesis, leading to apoptotic cell death. Moxetumomab pasudotox has been granted Orphan Drug Designation by the FDA and Orphan Designation by the European Medicines Agency for the treatment of HCL.
About Hairy Cell Leukaemia
HCL is a rare, incurable slow-growing leukaemia in which the bone marrow overproduces abnormal B cells or lymphocytes.6HCL can result in serious and life-threatening conditions, including infections, bleeding and anaemia.7 Approximately 1,000 people are diagnosed with HCL in the US each year.8,9,10 While many patients initially respond to treatment, up to 40% will relapse.11 With no established standard of care and very few treatments available, there remains significant unmet medical need for people with relapsed or refractory HCL.12,13
About the ‘1053’ Phase III Trial
The ‘1053’ trial is a single-arm, multicentre Phase III clinical trial assessing the efficacy, safety, immunogenicity and pharmacokinetics of moxetumomab pasudotox monotherapy in patients with relapsed or refractory HCL who have received at least two prior therapies. The trial is being conducted in 80 patients across 34 sites in 14 countries.14 The primary endpoint was durable complete response (CR), defined as CR with haematologic remission (blood count normalisation) for >180 days. Secondary outcome measures included overall response rate, relapse free survival, progression-free survival, time to response, safety, pharmacokinetic and immunogenic potential.14
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
About AstraZeneca in Haematology
Leveraging its collective heritage in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus, and is accelerating development of a broad portfolio of potential blood cancer treatments. AstraZeneca and Acerta Pharma, its haematology research and development centre of excellence, received US FDA approval for the first medicine in this franchise, Calquence (acalabrutinib), in 2017.
About MedImmune
MedImmune is the global biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across Oncology, Respiratory, Cardiovascular, Renal & Metabolic Diseases, and Infection and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD, one of AstraZeneca’s three global R&D centres, with additional sites in Cambridge, UK and South San Francisco, CA. For more information, please visit www.medimmune.com.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas – Oncology, Cardiovascular, Renal & Metabolism and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.
CONTACTS
Media Relations |
|
|
Karen Birmingham | UK/Global | +44 203 749 5634 |
Rob Skelding | UK/Global | +44 203 749 5821 |
Matt Kent | UK/Global | +44 203 749 5906 |
Gonzalo Viña | UK/Global | +44 203 749 5916 |
Jacob Lund | Sweden | +46 8 553 260 20 |
Michele Meixell | US | +1 302 885 2677 |
Investor Relations | ||
Thomas Kudsk Larsen | +44 203 749 5712 | |
Josie Afolabi | +44 7970 620 449 | |
Craig Marks | Finance, Fixed Income, M&A | +44 7881 615 764 |
Henry Wheeler | Oncology | +44 203 749 5797 |
Mitchell Chan | Oncology; Other | +1 240 477 3771 |
Christer Gruvris | Brilinta; Diabetes | +44 203 749 5711 |
Nick Stone | Respiratory; Renal | +44 203 749 5716 |
Jennifer Kretzmann | Retail investors | +44 203 749 5824 |
US Toll-Free | +1 866 381 7277 |
References
1 Kreitman, R, Dearden C, Zinzani P, Delgado J et al. Moxetumomab Pasudotox in Heavily Pretreated Patients with Relapsed/Refractory Hairy Cell Leukemia: Results of a Pivotal International Study. Oral presentation at: American Society of Clinical Oncology 2018; June 2018; Chicago, IL. Abstract #7004
2 Leukemia & Lymphoma Society. Glossary Results – Minimal Residual Disease. http://www.lls.org/llssearch?search-terms=minimal+residual+disease&search_language=en Accessed April 2018.
3 Thomas, Deborah A., Ravandi, F. et al. Importance of minimal residual disease in hairy cell leukemia: monoclonal antibodies as a therapeutic strategy. Leuk Lymphoma. 2009 Oct; 50(0 1): 27–31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109291/ Accessed April 2018.
4 G Aruna. Immunotoxins: A review of their use in cancer treatment. J Stem Cells Regn Med. 2006; 1(1): 31-36. Published online 2006 Dec 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907961/ Accessed April 2018.
5 Park JH, Ross LL. Targeted Immunotherapy for Hairy cell leukemia. Journ Clin Onc 2012; 30: 1888–1890. http://ascopubs.org/doi/abs/10.1200/JCO.2011.39.8313. Accessed April 2018.
6 National Institutes of Health. Hairy Cell Leukemia. https://rarediseases.info.nih.gov/diseases/6560/hairy-cell-leukemiaAccessed April 2018.
7 Hairy Cell Leukemia Foundation. Complications. https://www.hairycellleukemia.org/about-hcl/complications/ Accessed April 2018.
8Troussard X, Cornet E. Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment. AM J Hematol. 2017; 92(12):1382-1390. Published online 2017 Nov 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698705/ Accessed April 2018.
9 Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes. CA Cancer J Clin. 2016; 66:443-459. https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21357 Accessed April 2018.
10 Grever MR, Blachly JS, Andritsos LA. Hairy cell leukemia: Update on molecular profiling and therapeutic advances. Blood. 2014; 28(5):197-203. https://www.sciencedirect.com/science/article/pii/S0268960X14000514 Accessed April 2018.
11 Hairy Cell Leukemia Foundation. Treatment. https://www.hairycellleukemia.org/about-hcl/treatment/ Accessed April 2018.
12 López-Rubio, M., Garcia-Marco, J. A. Current and emerging treatment options for hairy cell leukemia. OncoTargets and Therapy. 2015; 8: 2147–2156. http://doi.org/10.2147/OTT.S70316 Accessed April 2018.
13 National Institutes of Health. Hairy Cell Leukemia. https://rarediseases.info.nih.gov/diseases/6560/hairy-cell-leukemia Accessed December 2017
14 ClinicalTrials.gov. Moxetumomab pasudotox for Advanced Hairy Cell Leukemia. https://clinicaltrials.gov/ct2/show/study/NCT01829711?term=moxetumomab&rank=4&show_locs=Y#locn Accessed April 2018.
SOURCE: AstraZeneca
- Digi Communications N.V. announced that its Spanish subsidiary, Digi Spain Telecom S.L.U., has completed the first stage of selling a Fibre-to-the-Home (FTTH) network in 12 Spanish provinces
- Natural Cotton Color lancia la collezione "Calunga" a Milano
- Astor Asset Management 3 Ltd: Salinas Pliego Incumple Préstamo de $110 Millones USD y Viola Regulaciones Mexicanas
- Astor Asset Management 3 Ltd: Salinas Pliego Verstößt gegen Darlehensvertrag über 110 Mio. USD und Mexikanische Wertpapiergesetze
- ChargeEuropa zamyka rundę finansowania, której przewodził fundusz Shift4Good tym samym dokonując historycznej francuskiej inwestycji w polski sektor elektromobilności
- Strengthening EU Protections: Robert Szustkowski calls for safeguarding EU citizens’ rights to dignity
- Digi Communications NV announces the release of H1 2024 Financial Results
- Digi Communications N.V. announces that conditional stock options were granted to a director of the Company’s Romanian Subsidiary
- Digi Communications N.V. announces Investors Call for the presentation of the H1 2024 Financial Results
- Digi Communications N.V. announces the conclusion of a share purchase agreement by its subsidiary in Portugal
- Digi Communications N.V. Announces Rating Assigned by Fitch Ratings to Digi Communications N.V.
- Digi Communications N.V. announces significant agreements concluded by the Company’s subsidiaries in Spain
- SGW Global Appoints Telcomdis as the Official European Distributor for Motorola Nursery and Motorola Sound Products
- Digi Communications N.V. announces the availability of the instruction regarding the payment of share dividend for the 2023 financial year
- Digi Communications N.V. announces the exercise of conditional share options by the executive directors of the Company, for the year 2023, as approved by the Company’s Ordinary General Shareholders’ Meetings from 18th May 2021 and 28th December 2022
- Digi Communications N.V. announces the granting of conditional stock options to Executive Directors of the Company based on the general shareholders’ meeting approval from 25 June 2024
- Digi Communications N.V. announces the OGMS resolutions and the availability of the approved 2023 Annual Report
- Czech Composer Tatiana Mikova Presents Her String Quartet ‘In Modo Lidico’ at Carnegie Hall
- SWIFTT: A Copernicus-based forest management tool to map, mitigate, and prevent the main threats to EU forests
- WickedBet Unveils Exciting Euro 2024 Promotion with Boosted Odds
- Museum of Unrest: a new space for activism, art and design
- Digi Communications N.V. announces the conclusion of a Senior Facility Agreement by companies within Digi Group
- Digi Communications N.V. announces the agreements concluded by Digi Romania (formerly named RCS & RDS S.A.), the Romanian subsidiary of the Company
- Green Light for Henri Hotel, Restaurants and Shops in the “Alter Fischereihafen” (Old Fishing Port) in Cuxhaven, opening Summer 2026
- Digi Communications N.V. reports consolidated revenues and other income of EUR 447 million, adjusted EBITDA (excluding IFRS 16) of EUR 140 million for Q1 2024
- Digi Communications announces the conclusion of Facilities Agreements by companies from Digi Group
- Digi Communications N.V. Announces the convocation of the Company’s general shareholders meeting for 25 June 2024 for the approval of, among others, the 2023 Annual Report
- Digi Communications NV announces Investors Call for the presentation of the Q1 2024 Financial Results
- Digi Communications intends to propose to shareholders the distribution of dividends for the fiscal year 2023 at the upcoming General Meeting of Shareholders, which shall take place in June 2024
- Digi Communications N.V. announces the availability of the Romanian version of the 2023 Annual Report
- Digi Communications N.V. announces the availability of the 2023 Annual Report
- International Airlines Group adopts Airline Economics by Skailark ↗️
- BevZero Spain Enhances Sustainability Efforts with Installation of Solar Panels at Production Facility
- Digi Communications N.V. announces share transaction made by an Executive Director of the Company with class B shares
- BevZero South Africa Achieves FSSC 22000 Food Safety Certification
- Digi Communications N.V.: Digi Spain Enters Agreement to Sell FTTH Network to International Investors for Up to EUR 750 Million
- Patients as Partners® Europe Announces the Launch of 8th Annual Meeting with 2024 Keynotes and Topics
- driveMybox continues its international expansion: Hungary as a new strategic location
- Monesave introduces Socialised budgeting: Meet the app quietly revolutionising how users budget
- Digi Communications NV announces the release of the 2023 Preliminary Financial Results
- Digi Communications NV announces Investors Call for the presentation of the 2023 Preliminary Financial Results
- Lensa, един от най-ценените търговци на оптика в Румъния, пристига в България. Първият шоурум е открит в София
- Criando o futuro: desenvolvimento da AENO no mercado de consumo em Portugal
- Digi Communications N.V. Announces the release of the Financial Calendar for 2024
- Customer Data Platform Industry Attracts New Participants: CDP Institute Report
- eCarsTrade annonce Dirk Van Roost au poste de Directeur Administratif et Financier: une décision stratégique pour la croissance à venir
- BevZero Announces Strategic Partnership with TOMSA Desil to Distribute equipment for sustainability in the wine industry, as well as the development of Next-Gen Dealcoholization technology
- Digi Communications N.V. announces share transaction made by a Non-Executive Director of the Company with class B shares
- Digi Spain Telecom, the subsidiary of Digi Communications NV in Spain, has concluded a spectrum transfer agreement for the purchase of spectrum licenses
- Эксперт по торговле акциями Сергей Левин запускает онлайн-мастер-класс по торговле сырьевыми товарами и хеджированию
- Digi Communications N.V. announces the conclusion by Company’s Portuguese subsidiary of a framework agreement for spectrum usage rights
- North Texas Couple Completes Dream Purchase of Ouray’s Iconic Beaumont Hotel
- Предприниматель и филантроп Михаил Пелег подчеркнул важность саммита ООН по Целям устойчивого развития 2023 года в Нью-Йорке
- Digi Communications NV announces the release of the Q3 2023 Financial Results
- IQ Biozoom Innovates Non-Invasive Self-Testing, Empowering People to Self-Monitor with Laboratory Precision at Home
- BevZero Introduces Energy Saving Tank Insulation System to Europe under name “BevClad”
- Motorvision Group reduces localization costs using AI dubbing thanks to partnering with Dubformer
- Digi Communications NV Announces Investors Call for the Q3 2023 Financial Results
- Jifiti Granted Electronic Money Institution (EMI) License in Europe
- Предприниматель Михаил Пелег выступил в защиту образования и грамотности на мероприятии ЮНЕСКО, посвящённом Международному дню грамотности
- VRG Components Welcomes New Austrian Independent Agent
- Digi Communications N.V. announces that Digi Spain Telecom S.L.U., its subsidiary in Spain, and abrdn plc have completed the first investment within the transaction having as subject matter the financing of the roll out of a Fibre-to-the-Home (“FTTH”) network in Andalusia, Spain
- Продюсер Михаил Пелег, как сообщается, работает над новым сериалом с участием крупной голливудской актрисы
- Double digit growth in global hospitality industry for Q4 2023
- ITC Deploys Traffic Management Solution in Peachtree Corners, Launches into United States Market
- Cyviz onthult nieuwe TEMPEST dynamische controlekamer in Benelux, Nederland
- EU-Funded CommuniCity Launches its Second Open Call
- Astrologia pode dar pistas sobre a separação de Sophie Turner e Joe Jonas
- La astrología puede señalar las razones de la separación de Sophie Turner y Joe Jonas
- Empowering Europe against infectious diseases: innovative framework to tackle climate-driven health risks
- Montachem International Enters Compostable Materials Market with Seaweed Resins Company Loliware
- Digi Communications N.V. announces that its Belgian affiliated companies are moving ahead with their operations
- Digi Communications N.V. announces the exercise of conditional share options by an executive director of the Company, for the year 2022, as approved by the Company’s Ordinary General Shareholders’ Meeting from 18 May 2021
- Digi Communications N.V. announces the availability of the instruction regarding the payment of share dividend for the 2022 financial year
- Digi Communications N.V. announces the availability of the 2022 Annual Report
- Digi Communications N.V. announces the general shareholders’ meeting resolutions from 18 August 2023 approving amongst others, the 2022 Annual Accounts
- Русские эмигранты усиливают призывы «Я хочу, чтобы вы жили» через искусство
- BevZero Introduces State-of-the-Art Mobile Flash Pasteurization Unit to Enhance Non-Alcoholic Beverage Stability at South Africa Facility
- Russian Emigrés Amplify Pleas of “I Want You to Live” through Art
- Digi Communications NV announces the release of H1 2023 Financial Results
- Digi Communications NV Announces Investors Call for the H1 2023 Financial Results
- Digi Communications N.V. announces the convocation of the Company’s general shareholders meeting for 18 August 2023 for the approval of, among others, the 2022 Annual Report
- “Art Is Our Weapon”: Artists in Exile Deploy Their Talents in Support of Peace, Justice for Ukraine
- Digi Communications N.V. announces the availability of the 2022 Annual Financial Report
- “AmsEindShuttle” nuevo servicio de transporte que conecta el aeropuerto de Eindhoven y Ámsterdam
- Un nuovo servizio navetta “AmsEindShuttle” collega l’aeroporto di Eindhoven ad Amsterdam
- Digi Communications N.V. announces the conclusion of an amendment agreement to the Facility Agreement dated 26 July 2021, by the Company’s Spanish subsidiary
- Digi Communications N.V. announces an amendment of the Company’s 2023 financial calendar
- iGulu F1: Brewing Evolution Unleashed
- Почему интерактивная «Карта мира» собрала ключевые антивоенные сообщества россиян по всему миру и становится для них важнейшим инструментом
- Hajj Minister meets EU ambassadors to Saudi Arabia
- Online Organizing Platform “Map of Peace” Emerges as Key Tool for Diaspora Activists
- Digi Communications N.V. announces that conditional stock options were granted to executive directors of the Company based on the general shareholders’ meeting approval from 18 May 2021
- Digi Communications N.V. announces the release of the Q1 2023 financial results
- AMBROSIA – A MULTIPLEXED PLASMO-PHOTONIC BIOSENSING PLATFORM FOR RAPID AND INTELLIGENT SEPSIS DIAGNOSIS AT THE POINT-OF-CARE
- Digi Communications NV announces Investors Call for the Q1 2023 Financial Results presentation
- Digi Communications N.V. announces the amendment of the Company’s 2023 financial calendar
- Digi Communications N.V. announces the conclusion of two Facilities Agreements by the Company’s Romanian subsidiary
- Digi Communications N.V. announces the conclusion of a Senior Facility Agreement by the Company’s Romanian subsidiary
- Patients as Partners Europe Returns to London and Announces Agenda Highlights
- GRETE PROJECT RESULTS PRESENTED TO TEXTILE INDUSTRY STAKEHOLDERS AT INTERNATIONAL CELLULOSE FIBRES CONFERENCE
- Digi Communications N.V. announces Digi Spain Telecom S.L.U., its subsidiary in Spain, entered into an investment agreement with abrdn to finance the roll out of a Fibre-to-the-Home (FTTH) network in Andalusia, Spain
- XSpline SPA / University of Linz (Austria): the first patient has been enrolled in the international multicenter clinical study for the Cardiac Resynchronization Therapy DeliveRy guided by non-Invasive electrical and VEnous anatomy assessment (CRT-DRIVE)
- Franklin Junction Expands Host Kitchen® Network To Europe with Digital Food Hall Pioneer Casper
- Unihertz a dévoilé un nouveau smartphone distinctif, Luna, au MWC 2023 de Barcelone
- Unihertz Brachte ein Neues, Markantes Smartphone, Luna, auf dem MWC 2023 in Barcelona
- Editor's pick archive....