A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE (MAGNOLIA)

A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Phase 3 Study Comparing the Effect of Abelacimab vs. Dalteparin on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With GI/GU Associated VTE

This is a Phase 3, multicenter, open-label, blinded endpoint study to evaluate the effect of abelacimab relative to dalteparin on venous thromboembolism (VTE) recurrence and bleeding in patients with gastrointestinal (GI)/genitourinary (GU) cancer associated VTE (Magnolia)

Study Overview

• Status: Terminated
• Conditions: Venous Thromboembolism; Pulmonary Embolism; Deep Venous Thrombosis
• Intervention / Treatment: Biological: Abelacimab; Drug: Dalteparin

Detailed Description

Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. Patients with intact GI and GU cancer have increased bleeding risk with oral direct anticoagulants (DOACs), Guidelines advice caution with those DOACs or state preference for low molecular weight heparin (LMWH) in this population. The ANT-008 study will compare treatment with abelacimab monthly administration to LMWH daily subcutaneous (sc) administration over 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months

• Study Type: Interventional
• Enrollment (Actual): 417
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Epping, Victoria, Australia, 3076
      • Northern Health
• Austria
  • Neustadt, Austria, 2700
    • LK Wiener Neustadt
  • Vienna, Austria, 1090
    • Medical University of Vienna
• Canada
  • Calgary, Canada, T2N1N4
    • University Of Calgary
  • Marie, Canada, P6A0A8
    • Sault Area Hospital
  • Toronto, Canada, M5G 2C4
    • Toronto General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Hamilton Health Sciences, Juravinski Hospital and Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Instituite
    • Ottawa, Ontario, Canada, K1H BL6
      • Ottawa Hospital Research Instituite
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100038
    • Beijing Shijitan Hosp.
  • Ch’ang-ch’un, China, 130012
    • Jilin Province Tumor Hospital
  • Guangdong, China, 510280
    • Southern Medical University - Zhujiang Hospital
  • Guangzhou, China, 510655
    • The Sixth Affiliated Hospital of Sun Yat-Sen University
  • Guangzhou, China, 510515
    • Nanfang Hospital of Southern Medical University
  • Huizhou, China, 516001
    • Huizhou Municipal Central Hospital
  • Nanjing, China, 210006
    • Nanjing First Hospital
  • Tongzhou, China, 226361
    • Nantong Tumor Hospital (Tumor Hospital Affiliated to Nantong University )
  • Wenzhou, China, 325000
    • The First Affiliated Hospital of Wenzhou Medical University
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Wuhan, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science &Technology
  • Zhejiang, China, 314000
    • The Second Hospital of Jiaxing
• Czechia
  • Brno, Czechia, 65653
    • Masarykuv Onkologicky Ustav
  • Hradec Králové, Czechia, 50005
    • University hospital Hradec Králové
  • Prague, Czechia, 14059
    • Thomayerova nemocnice
  • Prague, Czechia, 128 08
    • Onkologická klinika VFN a 1. LF UK
• France
  • Angers, France, 49933
    • CHU Angers - Hôpital Hôtel Dieu
  • Clermont-Ferrand, France, 63003
    • CHU Clermont Ferrand - Hopital Gabriel Montpied
  • Limoges, France, 87042
    • CHU de Limoges - Hôpital Dupuytren
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere
  • Pierre-Bénite, France, 69310
    • Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
  • Rouen, France, 76031
    • CHU de Rouen - Hôpital de Bois Guillaume
  • Saint-Etienne, France, 42000
    • CHU de Saint-Étienne - Hôpital Nord
  • Strasbourg, France, 67091
    • CHU Strasbourg - Nouvel Hôpital Civil
  • Toulon, France, 83000
    • Centre Hospitalier Intercommunal de Toulon
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU de Nancy - Hôpital de Brabois Adultes
  • Cedex
    • Limoges, Cedex, France, 87042
      • CHU de Limoges - Hôpital Dupuytren
  • Chantemesse
    • Le Puy-en-Velay, Chantemesse, France, 43 000
      • CH Le puy en Velay
  • Renouiflers
    • Colombes, Renouiflers, France, 92700
      • Hopital Louis Mourier
  • Rue Du Morvan
    • Vandœuvre-lès-Nancy, Rue Du Morvan, France, 54500
      • CHU de Nancy - Hôpital de Brabois Adultes
  • Strasbourg
    • Strasbourg, Strasbourg, France, 67091
      • Nouvel Hôpital Civil de Strasbourg
• Germany
  • Dresden, Germany, 1307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Dresden, Germany, 01067
    • Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
  • Görlitz, Germany, 2827
    • Praxis für Gefäßmedizin
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf
  • Leipzig, Germany, 4103
    • Universitätsklinik Leipzig
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
  • Eger, Hungary, H-3300
    • Markhot Ferenc Oktatokorhaz és Rendelointezet
• Ireland
  • Cork, Ireland, T12 DC4A
    • Cork University Hospital
  • Cork, Ireland, T12 DV56
    • Bon Secour Hospital
  • Dublin, Ireland, D09V2N0
    • Beaumont Hospital
• Italy
  • Bari, Italy, 70124
    • IRCCS Istituto Tumori Giovanni Paolo II
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni xxiii
  • Bologna, Italy, 40133
    • Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
  • Castelfranco Veneto, Italy, 31033
    • Presidio Ospedaliero di Castelfranco Veneto
  • Chieti, Italy, 66013
    • SS. ma Annunziata
  • Cosenza, Italy, 87100
    • Ospedale Civile Dell Annunziata
  • Faenza, Italy, 48018
    • Ospedale degli Infermi
  • Milan, Italy, 20142
    • Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori Fondazione G. Pascale
  • Padova, Italy, 35128
    • Azienda Ospedale - Università Padova
  • Padova, Italy, 35128
    • Ospedale Universitario
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Vicenza, Italy, 36100
    • Ospedale San Bortolo di Vicenza
• Latvia
  • Daugavpils, Latvia, LV-5417
    • Daugavpils Regional Hospital
  • Liepāja, Latvia, LV3414
    • Liepaja Regional Hospital
  • Riga, Latvia, LV-1002
    • Pauls Stradins CUH
• Netherlands
  • Amersfoort, Netherlands, 3813
    • Meander Medisch Centrum
  • Dordrecht, Netherlands, 3317 NM
    • Albert Schweitzer Ziekenhuis, Dordwijk
  • Haarlem, Netherlands
    • Spaarne Gasthuis (Kennemer Gasthuis) - Haarlem-Zuid
  • Holland, Netherlands, 1105AZ
    • Amsterdam University Medical Center
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Nijmegen, Netherlands, 6500
    • Radboud Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
  • The Hague, Netherlands, 2545 AA
    • Haga Ziekenhuis
• Norway
  • Fredrikstad, Norway, 1603
    • Østfold Hospital Kalnes
  • Lørenskog, Norway, 1478
    • Akershus Univeristy Hospital
• South Korea
  • Jeonju, South Korea, 54907
    • Jeonbuk National University Hospital
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 7985
    • Ewha Womans University Mokdong Hospital
• Spain
  • Alicante, Spain, 03293
    • Hospital Universitario del Vinalopó
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Elche, Spain, 3203
    • Hospital General Universitario de Elche
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves
  • Jaén, Spain, 23007
    • Hospital Universitario Ciudad de Jaen
  • Lugo, Spain, 27003
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28033
    • Md Anderson Cancer Centre
  • Majadahonda, Spain, 28222
    • Hospital Universitario Puerta De Hierro Majadahonda
  • Ourense, Spain
    • Complejo Hospitalario Universitario De Ourense
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturia
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sabadell, Spain, 8208
    • Corporacio Sanitaria Parc Tauli
  • Santander, Spain, 39012
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocío
• Sweden
  • Sundsvall, Sweden, 85186
    • Länssjukhuset Sundsvall-Härnösand
• Switzerland
  • Geneva, Switzerland, 1205
    • Hopital Universitaire Geneve
• Taiwan
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University (NCKU) Hospital
  • Taipei, Taiwan, 11490
    • Tri-Service General Hospital
• United Kingdom
  • ENG
    • Cottingham, ENG, United Kingdom, HU16 5JQ
      • Castle Hill Hospital, Department of Oncology & Haematology
    • Newcastle upon Tyne, ENG, United Kingdom, NE7 7DN
      • The Newcastle Upon Tyne Hospitals
  • England
    • Cardiff, England, United Kingdom, CF14 4XW
      • University Hospital of Wales
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20422
      • Washington DC VAMC
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Cancer Center-Middletown
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center-Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center-West Harrison
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10021-0005
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female subjects ≥18 years old or other legal maturity age according to the country of residence

• Confirmed GI (colorectal, pancreatic, gastric, esophageal, gastro-esophageal junction or hepatobiliary) or confirmed GU (renal, ureteral, bladder, prostate, or urethra) cancers if:

  • Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
  • No intended curative surgery during the study
• Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
• Anticoagulation therapy with LMWH for at least 6 months is indicated
• Able to provide written informed consent

Exclusion Criteria:

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) occurrence of DVT and/or PE
• More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other anticoagulants
• An indication to continue treatment with therapeutic doses of an anticoagulant other than for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE)
• PE leading to hemodynamic instability (systolic BP <90 mmHg or shock).
• Acute ischemic or hemorrhagic stroke or intracranial hemorrhage, in the last 4 weeks preceding screening.
• Brain trauma, or cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
• Need for aspirin in a dosage of more than 100 mg/day or, any other antiplatelet agent alone or in combination with aspirin
• Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
• Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
• History of heparin induced thrombocytopenia
• Infective acute or subacute endocarditis at the time of presentation
• Primary brain cancer or untreated intracranial metastasis
• Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
• Life expectancy of <3 months at randomization
• Calculated creatinine clearance (CrCl) <30 mL/min at the screening visit
• Platelet count <50,000/ mm3 at the screening visit
• Hemoglobin <8 g/dL at the screening visit
• Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase ≥3 times and/or bilirubin ≥2 times the upper limit of normal (ULN) at the screening visit in the absence of clinical explanation
• Uncontrolled hypertension (systolic blood pressure [BP] > 180 mm Hg or diastolic BP >100 mm Hg despite antihypertensive treatment)
• Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
• Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
• Pregnant or breast-feeding women
• History of hypersensitivity to any of the study drugs (including dalteparin) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for dalteparin
• Subjects with any condition that in the judgement of the Investigator would place the subject at increased risk of harm if he/she participated in the study
• Use of other investigational (not-registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abelacimab; Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously	Biological: Abelacimab; Abelacimab 150 mg; Other Names: MAA868
Active Comparator: Dalteparin; Dalteparin administered subcutaneously daily	Drug: Dalteparin; Dalteparin 200 IU/kg/day followed by 150 IU/kg/day; Other Names: Fragmin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of centrally adjudicated VTE recurrence	Time to first adjudicated venous thromboembolism (VTE) event recurrence	up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events	Time to first adjudicated major or clinically relevant non-major (CRNM) bleeding event	up to 6 months
Time to first event of VTE recurrence, ISTH adjudicated major or ISTH-adjudicated CRNM bleeding events	Time to first adjudicated venous thromboembolism (VTE) or bleeding event	up to 6 months
Time to event of permanent treatment discontinuation not due to death	Time to permanent discontinuation not due to death	up to 6 months
Time to first event of ISTH-adjudicated CRNM bleeding events	Time to first adjudicated clinically relevant non-major (CRNM) bleeding event	up to 6 months
Time to first event of ISTH-adjudicated major bleeding events	Time to first adjudicated major bleeding event	Up to 6 months
Time to first event of GI ISTH-adjudicated major and GI CRNM bleeding events	Time to first adjudicated gastrointestinal (GI) major and clinically relevant non-major (CRNM) bleeding event	up to 6 months
All-cause death, vascular death, serious adverse events, adverse events leading to drug discontinuation, other adverse events, abnormal lab tests, etc. presented as rate per 100 patient-years		up to 6 months
For patients treated with abelacimab: percent with injection site reactions/severity, hypersensitivity reactions/severity, anti-drug antibody formation, neutralizing antibody		up to 6 months

Collaborators and Investigators

• Sponsor: Anthos Therapeutics, Inc.
• Collaborators: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2022
• Primary Completion (Actual): April 10, 2026
• Study Completion (Actual): April 10, 2026

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): December 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: GI cancer; Anticoagulants; LMWH; CAT; VTE recurrence rate; PROBE design; Cancer associated VTE; Abelacimab; FXI; Major bleeding events; CRNM bleeding events; Dalteparin; GU cancer
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Thrombosis; Pulmonary Embolism; Venous Thrombosis; Gastrointestinal Neoplasms; Venous Thromboembolism; Carbohydrates; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Dalteparin; abelacimab; MAA868
• Other Study ID Numbers: ANT-008; 2021-003085-12 (EudraCT Number); CMAA868D12301 (Other Identifier: Novartis code)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No