Abelacimab vs Dalteparin for Blood Clot Prevention in Cancer Patients

(MAGNOLIA Trial)

Recruiting at 132 trial locations

Overseen By John McRae

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Anthos Therapeutics, Inc.

Must be taking: Anticoagulants

Must not be taking: Antiplatelets, Fibrinolytics

Disqualifiers: Stroke, Brain cancer, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

1020 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, abelacimab (an FXI antibody) and dalteparin, to determine which better prevents blood clots in people with certain cancers, such as those affecting the stomach or urinary areas. Blood clots pose significant risks for cancer patients, so identifying the best prevention method is crucial. Suitable candidates for this trial include individuals with stomach or urinary cancer who have recently experienced a blood clot in their leg or lung. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you do not have an indication to continue treatment with other anticoagulants besides those for VTE treatment. If you are on other anticoagulants for conditions like atrial fibrillation, you may need to stop them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abelacimab is likely safe. Studies have found it effective in preventing blood clots after knee surgery, with a low risk of causing bleeding. This is significant because bleeding is a common concern with blood-thinning treatments. Abelacimab works differently from other blood thinners, which may contribute to its safety.

Dalteparin is well-known and approved by the FDA for preventing blood clots in cancer patients. Its long history of use suggests it is generally safe when used correctly.

In summary, both treatments in this study are well-tolerated. Abelacimab has demonstrated a low risk of bleeding in studies, and dalteparin has a proven safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Abelacimab is unique because it targets blood clots in a different way than traditional treatments like dalteparin. While most standard treatments involve daily administration, Abelacimab offers the convenience of a monthly dose after an initial intravenous administration. This not only simplifies the treatment regimen but also potentially improves compliance among patients. Researchers are excited about Abelacimab because its novel mechanism of action could offer more effective prevention of blood clots in cancer patients, reducing the burden of frequent injections.

What evidence suggests that this trial's treatments could be effective for preventing blood clots in cancer patients?

Research has shown that abelacimab, which participants in this trial may receive, effectively prevents blood clots in veins (venous thromboembolism or VTE) in cancer patients. Studies suggest it could be a promising new blood thinner with a lower risk of bleeding compared to other treatments. Abelacimab has also proven effective in preventing VTE after surgeries like knee replacements, indicating potential benefits for cancer patients with blood clots. In contrast, dalteparin, another treatment option in this trial, is already a standard treatment for preventing blood clots in cancer patients. Both treatments in this trial aim to reduce the risk of clots while maintaining low bleeding risks. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with gastrointestinal or genitourinary cancer who have had a recent deep vein thrombosis or pulmonary embolism. They must be able to take blood thinners for at least 6 months and not have any planned major surgery, brain trauma, severe liver issues, uncontrolled high blood pressure, or a life expectancy under 3 months.

Inclusion Criteria

I was diagnosed with a blood clot in my leg or lung within the last 5 days.

Able to provide written informed consent

I have been on blood thinner medication for at least 6 months.

Exclusion Criteria

I have had a blood clot in my lung that affected my heart's ability to pump blood.

I have been on blood thinners for more than 5 days.

I have had bleeding that needed medical attention in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either abelacimab monthly or dalteparin daily for 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abelacimab
• Dalteparin

Trial Overview The study compares Abelacimab to Dalteparin in preventing blood clot recurrence and managing bleeding risks in patients with certain cancers. It's an open-label trial where the effects of each treatment are evaluated by researchers unaware of which group participants belong to.

How Is the Trial Designed?

Group I: Abelacimab Experimental Treatment 1 Intervention

Abelacimab intravenous administration followed by monthly administration of the same dose subcutaneously

Group II: Dalteparin Active Control 1 Intervention

Dalteparin administered subcutaneously daily

Who Is Running the Clinical Trial?

Anthos Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

6,600+

Itreas

Collaborator

Trials

2

Recruited

2,700+

Published Research Related to This Trial

Abelacimab, a novel monoclonal antibody targeting Factor XI, demonstrated significant reductions in free FXI levels (over 99%) after intravenous administration, indicating its strong anticoagulant effect.

The drug was found to be safe and well-tolerated in both healthy volunteers and patients with atrial fibrillation, with no clinically relevant bleeding events reported, supporting its potential for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa. Yi, BA., Freedholm, D., Widener, N., et al.[2023]

In a review of four randomized studies involving new oral anticoagulants (NOACs) for treating venous thromboembolism (VTE) in cancer patients, all three FXa inhibitors (rivaroxaban, edoxaban, and apixaban) were found to be as effective as the standard treatment, dalteparin, with lower VTE recurrence rates for rivaroxaban (-5.0%) and edoxaban/apixaban (-2.3%).

While rivaroxaban and edoxaban showed an increased risk of severe bleeding, particularly gastrointestinal bleeding, apixaban demonstrated a better safety profile with no increase in severe bleeding rates, suggesting it may be a safer option for patients with specific bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modern anticoagulation with factor Xa inhibitors in oncology: is the gastrointestinal bleeding rate (also) decisive?] Raithel, M., Haibach, M., Kremenevski, I., et al.[2023]

In a study of 280 metastatic melanoma patients treated with immune checkpoint inhibitors (ICI), those receiving the oral FXa inhibitor rivaroxaban showed significantly improved clinical outcomes, including higher complete response rates and better progression-free survival compared to those not on FXa inhibitors.

Patients on anticoagulation during ICI therapy did not experience increased bleeding complications, suggesting that FXa inhibitors can be safely combined with ICI therapy to potentially enhance anti-tumor immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticoagulation with Factor Xa Inhibitors Is Associated with Improved Overall Response and Progression-Free Survival in Patients with Metastatic Malignant Melanoma Receiving Immune Checkpoint Inhibitors-A Retrospective, Real-World Cohort Study. Haist, M., Stege, H., Pemler, S., et al.[2021]

In the SELECT-D trial, rivaroxaban demonstrated lower rates of venous thromboembolism (VTE) recurrence compared to dalteparin, but it was associated with a higher risk of bleeding in cancer patients.

A cost-effectiveness analysis showed that rivaroxaban is economically dominant over dalteparin, potentially saving over €10 million annually for approximately 8000 cancer patients with VTE in the Netherlands, while also slightly improving patient health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent venous thromboembolism. de Jong, LA., van der Velden, AWG., Hulst, MV., et al.[2021]

In a study using adult wild-type CD1 mice, treatment with the anti-factor XI monoclonal antibody 14E11 significantly reduced thrombus weight and volume after deep vein thrombosis (DVT) induction, suggesting its potential efficacy in enhancing thrombus resolution.

14E11 treatment also led to changes in inflammatory markers, including reduced circulating monocytes and macrophage content in thrombi, indicating that targeting FXI may not only aid in clot resolution but also modulate inflammation during the recovery process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis. Jordan, KR., Wyatt, CR., Fallon, ME., et al.[2023]

In a study using xenograft models, the Factor Xa-targeting DOAC rivaroxaban and the thrombin-targeting DOAC dabigatran did not inhibit the growth or metastasis of human breast cancer cells, indicating that these anticoagulants may not have anticancer effects in this context.

Despite effectively prolonging coagulation times, neither rivaroxaban nor dabigatran showed any significant impact on tumor growth or metastasis in various breast cancer models, suggesting that their role in cancer treatment needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The direct oral anticoagulants rivaroxaban and dabigatran do not inhibit orthotopic growth and metastasis of human breast cancer in mice. Buijs, JT., Laghmani, EH., van den Akker, RFP., et al.[2023]

In the SELECT-D trial, extending anticoagulation with rivaroxaban for an additional 6 months after initial treatment significantly reduced the recurrence of venous thromboembolism (VTE) to 4% compared to 14% with placebo, although the study was underpowered with only 92 participants.

However, the use of rivaroxaban was associated with a 5% rate of major and clinically relevant non-major bleeding, indicating a potential safety concern when extending anticoagulation therapy in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m). Marshall, A., Levine, M., Hill, C., et al.[2023]

The select-d trial is a pioneering study comparing the effectiveness of rivaroxaban and dalteparin in preventing recurrent venous thromboembolism (VTE) in cancer patients, with 530 participants being recruited to ensure reliable outcome estimates.

Preliminary data shows that most participants have solid tumors, with a significant portion presenting with incidental pulmonary embolism, highlighting the need for targeted treatment strategies in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OC-11 - Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. Young, A., Phillips, J., Hancocks, H., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11262452/

Abelacimab in Cancer-Associated Thrombosis: The Right ... Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients.

2. drugtargetreview.com drugtargetreview.com/article/157508/abelacimab-the-next-frontier-in-safer-anticoagulation-therapy/

Abelacimab: the next frontier in safer anticoagulation therapy Abelacimab represents a breakthrough in drug discovery, offering a novel approach to anticoagulation that could potentially prevent strokes with minimal ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2105872

Abelacimab for Prevention of Venous Thromboembolism Abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-comparing-abelacimab-and-apixaban-for-preventing-blood-clots-in-cancer-patients/

Study Comparing Abelacimab and Apixaban for Preventing ... This study compares the efficacy of Abelacimab and Apixaban in preventing venous thromboembolism recurrence in cancer patients over a ...

5. anthostherapeutics.com anthostherapeutics.com/press-release/anthos_2024-08-15_release-8/

Anthos Therapeutics Launches Second Phase 3 Clinical ... The MAGNOLIA study will compare abelacimab against the current standard of care for VTE in cancer associated thrombosis (CAT) in patients with GI/GU cancers.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2590257124000063

A leap forward in anticoagulation with FXI and FXIa Inhibition Abelacimab, an antibody that inhibits FXI, has shown potential in transforming anticoagulation therapy by sparing hemostasis. This review provides a ...