Treatment and Secondary Prevention of Venous Thromboembolism (VTE) in Adult Participants With Solid and Hematologic Cancers

Official title

A 2-Part, Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study to Assess Efficacy and Safety of REGN7508, a Monoclonal Antibody Against Factor XI, for the Treatment and Secondary Prevention of Venous Thromboembolism in Participants With Solid and Hematologic Cancers (ROXI-CAT-II)

Overview

This study is researching an experimental drug called REGN7508 (called "study drug") and will consist of 2 parts: Part 1 and Part 2. The study is focused on participants with or without cancer who develop blood clots in certain veins (called Deep Vein Thrombosis \[DVT\]) that block blood flow (Part 1) or focused on participants with cancer who develop blood clots in certain veins (DVT) or the lungs (also called Pulmonary Embolism \[PE\]) (Part 2). The aim of the study is to see how safe and effective the study drug is at treating and preventing further blood clots in participants with or without cancer (Part 1) or in participants with cancer (Part 2) compared with another treatment (apixaban). The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Interventions

• Drug REGN7508
  Administered per the protocol
• Drug Apixaban
  Administered per the protocol

Primary outcome measures

• Occurrence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Approximately 6 months]
• Severity of TEAEs [Time frame: Approximately 6 months]
• Time-to-first event of centrally adjudicated recurrent VTE [DVT (symptomatic or asymptomatic [proximal] or Non-fatal PE (symptomatic or asymptomatic [in a segmental or larger pulmonary artery] )or VTE-related death)] [Time frame: Up to approximately 3.5 years]
• Time-to-first event of centrally adjudicated International Society of Thrombosis and Hemostasis (ISTH)-defined major bleeding or Clinically Relevant Non-Major (CRNM) bleeding [Time frame: Up to approximately 3.5 years]

Secondary outcome measures (12)

• Percent inhibition of Factor XI functional Coagulant activity (FXI:C) [Time frame: Approximately 3 months]
• Fold change from baseline in activated Partial Thromboplastin Time (aPTT) [Time frame: Approximately 3 months]
• Functional REGN7508 concentration [Time frame: Approximately 3 months]
• Factor XI (FXI) concentration [Time frame: Approximately 3 months]
• Occurrence of Anti-Drug Antibody (ADA) to REGN7508 [Time frame: Up to approximately 3.5 years]
• Magnitude of ADA to REGN7508 [Time frame: Up to approximately 3.5 years]
• Time-to-first centrally adjudicated event of DVT (symptomatic or asymptomatic [proximal]) [Time frame: Up to approximately 3.5 years]
• Time-to-first centrally adjudicated event of Non-fatal PE (symptomatic or asymptomatic [in a segmental or larger pulmonary artery]) [Time frame: Up to approximately 3.5 years]
• Time-to-first centrally adjudicated event of VTE-related death [Time frame: Up to approximately 3.5 years]
• Time-to-first event of centrally adjudicated venous thromboembolic events other than DVT and PE [Time frame: Up to approximately 3.5 years]
• Time-to-first event of centrally adjudicated Arterial Thromboembolism (ATE) [Time frame: Up to approximately 3.5 years]
• Time-to-first event of centrally adjudicated recurrent VTE and bleeding events [DVT (symptomatic or asymptomatic [proximal] or Non-fatal PE (symptomatic or asymptomatic) or VTE-related death) or bleeding (ISTH-defined major bleeding or CRNM bleeding)] [Time frame: Up to approximately 3.5 years]

Eligibility criteria

Inclusion criteria

• Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 at the time of screening and day 1 prior to first dose of study intervention
• In Part 1 participants with cancer and Part 2 participants: Histologically confirmed diagnosis of malignant solid or select hematologic tumor (other than basal-cell or squamous-cell carcinoma of the skin alone) as described in the protocol
• Part 1 additional criteria:

• Has newly diagnosed symptomatic lower extremity DVT or incidentally-detected proximal lower extremity DVT (eg, popliteal or femoral) within 5 days (120 hours) of randomization (with imaging confirmation)
• Anticoagulation therapy with a therapeutic dose of a Direct Oral Anticoagulant (DOAC) for at least 3 months is indicated for the newly diagnosed proximal lower extremity DVT
• Part 2 additional criteria:

• Newly diagnosed VTE within 5 days (120 hours) of randomization (with imaging confirmation) as described in the protocol
• Anticoagulation therapy with a therapeutic dose of a DOAC for at least 6 months is indicated for newly diagnosed VTE

Exclusion criteria

• Is at high risk of intracranial bleeding in the opinion of the investigator
• Known bleeding conditions (eg, Hemophilia A or B, von Willebrand's disease), hemorrhagic tumor sites, or other conditions with a high risk for bleeding (eg, hepatic disease associated with coagulopathy)
• Contraindication to anticoagulation in the opinion of the investigator
• Life expectancy of < 6 months
• Part 1 participants with cancer and Part 2 additional exclusion criteria:

• Has acute leukemia or myelodysplastic syndrome
• Has primary brain tumor
• Has brain metastases as described in the protocol
• Part 1 additional exclusion criteria:

• Has a symptomatic PE
• Has an asymptomatic (incidentally-diagnosed) PE in a segmental or larger pulmonary artery
• Part 2 additional exclusion criteria: PE leading to hemodynamic instability as described in the protocol

Note: Other Protocol Defined Inclusion/ Exclusion Criteria Apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Bioresearch Partner- Hialeah Hospital — Hialeah
• El Paso Medical Research Institute (Medresearch Inc) — El Paso

South Korea · 2 centers

• Haeundae Paik Hospital — Pusan
• Severance Hospital — Seoul

Identifiers

NCT: NCT07493304 · R7508-CAT-2396 · 2024-519299-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗