Sponsor Decision

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)

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

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.

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