MAGNOLIA Study of Abelacimab for Cancer-Associated Thrombosis Initiates Recruitment

The phase 3 MAGNOLIA study has begun enrolling patients to examine abelacimab for the treatment of thrombosis associated with cancer.

Recruitment has begun in the MAGNOLIA study (NCT05171075) examining abelacimab (formerly, MAA868) in patients with gastrointestinal/genitourinary (GI/GU) who are at risk of thrombosis, according to Anthos Therapeutics.

Abelacimab is a dual-acting fully human monoclonal antibody that selectively targets Factor XI and Factor XIa with high affinity. Potentially, the antibody can achieve hemostasis-sparing anticoagulation and protect from thromboembolic events with a reduced risk of clinically significant bleeding compared to existing therapies.

Currently, abelacimab is being investigated in a phase 3 program in cancer-associated thrombosis (CAT), which includes 2 studies with a combined target enrollment of approximately 2700 patients. Between the 2 studies, patients will be evaluated at 220 treatment sites across 20 countries, making it the largest research program of any anticoagulant used for the treatment of cancer-associated thrombosis.

“Based on the positive phase 2 data we’ve seen to date; we are hopeful that this trial will validate the promise of abelacimab as a much-needed new treatment option for this high-risk and difficult-to-treat patient population. With a 20-fold increase in risk of cancer associated thrombosis in GI cancers compared to patients without cancer, we are particularly pleased that abelacimab is being explored to reduce VTE recurrence and bleeding in GI and GU cancers,” said Alok A. Khorana, MD, professor of medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University and member of the Abelacimab CAT Program Steering Committee, in the press release. “Because cancer patients who receive current anticoagulant treatment to manage VTE have a higher bleeding risk than patients without cancer receiving anticoagulants, it’s too often that physicians are forced to choose between preventing life-threatening clots, and putting their patients at risk of uncontrolled bleeding, particularly in patients with GI/GU cancers.”

Venous thromboembolism (VTE), including both deep vein thrombosis and pulmonary embolism is the second most common cause of death for patients with cancer. The currently available anticoagulants for the treatment of VTE can increase the risk of bleeding in patients, demonstrating an unmet medical need.

“The urgent need for this research and the development of effective and safer anticoagulants is underscored not only by the FDA’s recent fast track designation of abelacimab [for the treatment of thrombosis associated with cancer], but also by the passion and commitment of our CAT Scientific Steering Committee to the patients they treat,” said Dan Bloomfield, MD, chief medical officer at Anthos Therapeutics, in the press release.

To address this unmet medical need, the MAGNOLIA trial will evaluate monthly treatment with abelacimab vs once daily injection of dalteparin, the current anticoagulant standard of care in patients with GI/GU cancers. This study will assess the effects on venous thromboembolism (VTE) recurrence and bleeding in patients with cancer associated VTE, a leading cause of death in patients with cancer.

MAGNOLIA is an international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study. In the study, treatment with abelacimab will be compared with dalteparin in roughly 1020 patients with GI and GU cancers and associated VTE. Patients will be dosed with abelacimab 150 mg administered intravenously (IV) followed by monthly administration of the same dose subcutaneously (SC) for up to 6 months. In the control arm, patients will be administered dalteparin SC daily at 200 IU/kg/day for the first month, and then 150 IU/kg/day up to 6 months.1

Enrollment is open to patients aged 18 years old with unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancers with no intended curative surgery during the study. Patients must have a confirmed symptomatic or incidental proximal lower limb acute deep vein thrombosis and/or confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 72 hours from diagnosis of the qualifying VTE. Further, patients must have had anticoagulation therapy with low molecular weight heparin for at least 6 months.

MAGNOLIA will explore the primary end points of time to the first event of centrally adjudicated VTE recurrence consisting of new proximal deep venous thrombosis, new pulmonary embolism (PE), or fatal PE, including unexplained death. Secondary end points of the study include time to the first event of the International Society on Thrombosis and Haemostasis-adjudicated major or clinically relevant non-major bleeding events, and the net clinical benefit of abelacimab vs apixaban.

In the other phase 3 study, ASTER, treatment with abelacimab will be compared with apixaban for recurrence and bleeding in patients with cancer-associated VTE (NCT05171049).

The international multicenter, randomized, open-label, blinded endpoint evaluation, phase 3 study will enroll approximately 1655 patients. Those enrolled will be given abelacimab 150 mg via IV infusion on day 1 and SC monthly doses thereafter for up to 6 months in the experimental arm. Apixaban 10 mg will be administered orally, twice daily for the first 7 days, followed by 5 mg bid up to 6 months in the control arm.3

The primary end points of ASTER are the same as those in MAGNOLIA. Both studies of abelacimab are actively recruiting patients with cancer-associated VTE.

“Unfortunately, many patients at risk of thrombosis stop taking low molecular weight heparins, which require daily injections, after less than 2 months, and sadly patients don’t stay much longer on DOACs. Our hope is that the monthly dosing schedule of abelacimab and its potential enhanced safety profile will play a role in improving adherence and quality of life,” added Khorana.

References
  1. Anthos Therapeutics Launches Second Phase 3 Clinical Trial of Its Dual-acting Factor XI Inhibitor, Abelacimab. August 25, 2022. Accessed August 29, 2022. https://yhoo.it/3TpDqks
  2. A study comparing abelacimab to dalteparin in the treatment of gastrointestinal/genitourinary cancer and associated VTE (MAGNOLIA). Updated July 20, 2022. Accessed August 29, 2022.
  3. A study comparing abelacimab to apixaban in the treatment of cancer-associated VTE (ASTER). ClinicalTrial.gov. Updated August 22, 2022. Accessed August 29, 2022.