A multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 Study comparing the effect of abelacimab relaTive to apixaban on venous thromboEmbolism (VTE) recurrence and bleeding in patients with canceR associated VTE (ASTER)

This is a Phase 3,multicenter, randomized, open-label, blinded endpoint evaluation study
comparing the effect of abelacimab relative to apixaban on venous thromboembolism (VTE)
recurrence and bleeding in patients with cancer associated VTE (ASTER)

Inclusion Criteria:

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

- Confirmed diagnosis of cancer (by histology, adequate imaging modality), other than
basal-cell or squamous-cell carcinoma of the skin alone with one of the following:

- Active cancer, defined as either locally active, regionally invasive, or
metastatic cancer at the time of randomization and/or

- Currently receiving or having received anticancer therapy (radiotherapy,
chemotherapy, hormonal therapy, any kind of targeted therapy or any other
anticancer therapy) in the last 6 months.

- Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT)
(i.e., popliteal, femoral, iliac, and/or inferior vena cava [IVC] 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 a therapeutic dose of DOAC 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) DVT and/or PE

- More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH,
fondaparinux, DOAC, or other anticoagulants

- An indication to continue treatment with therapeutic doses of an anticoagulant other
than that VTE treatment prior to randomization (e.g., atrial fibrillation [AF],
mechanical heart valve, prior VTE)

- Platelet count <50,000/mm3 at the screening visit

- PE leading to hemodynamic instability (blood pressure [BP] <90 mmHg or shock)

- Acute ischemic or hemorrhagic stroke or intracranial hemorrhage within the 4 weeks
preceding screening

- Brain trauma or a cerebral or 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 >100 mg/day or any other antiplatelet agent alone or
in combination with aspirin

- Primary brain cancer or untreated intracranial metastases at baseline

- Acute myeloid or lymphoid leukemia

- 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

- Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening

- Life expectancy <3 months at randomization

- Calculated creatinine clearance (CrCl) <30 mL/min (Cockcroft-Gault equation) at the
screening visit

- Hemoglobin <8 g/dL at the screening visit

- Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine
aminotransferase (ALT) ≥3 x and/or bilirubin ≥2 x upper limit of normal (ULN) at the
screening visit in absence of clinical explanation

- Uncontrolled hypertension (systolic 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 apixaban or 100 days after administration of abelacimab (See Section
5.3.6. for highly effective contraceptive measures)

- 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
apixaban or 100 days after administration of abelacimab

- Pregnant or breast-feeding women

- Patients known to be receiving strong dual inducers or inhibitors of both CYP3A4 and P
gp

- History of hypersensitivity to any of the study drugs (including apixaban) or
excipients, to drugs of similar chemical classes, or any contraindication listed in
the label for apixaban

- Subjects with any condition that in the Investigator's judgement 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(s) (PD) 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