Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL) (BRUIN-MCL-321)

Loxo Oncology

Status and phase: Active, not recruiting; Phase 3

Conditions: Lymphoma, Mantle-Cell

Treatments: Drug: Ibrutinib; Drug: Pirtobrutinib; Drug: Acalabrutinib; Drug: Zanubrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04662255

J2N-OX-JZNM (Other Identifier)

LOXO-BTK-20019

Details and patient eligibility

About

This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.

Full description

This is a Phase 3 global, randomized, open-label study comparing pirtobrutinib (Arm A) to investigator's choice of ibrutinib, acalabrutinib or zanubrutinib (Arm B) in MCL patients who have received 1 or more lines of therapy and are BTK inhibitor naïve.

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Confirmed MCL diagnosis
• Previously treated with at least one prior line of systemic therapy for MCL
• Measurable disease per Lugano criteria
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Absolute neutrophil count ≥ 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening
• Hemoglobin ≥ 8 g/dL not requiring transfusion support or growth factors within 7 days of screening
• Platelets ≥ 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.
• AST and ALT ≤ 3.0 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN.
• Creatinine clearance of ≥ 30 mL/min according to Cockcroft/Gault Formula

Exclusion criteria

• Prior treatment with an approved or investigational BTK inhibitor
• History of bleeding diathesis
• History of stroke or intracranial hemorrhage within 6 months of randomization
• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization
• Clinically significant cardiovascular disease
• Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs
• Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible)
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption
• Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
• Vaccination with live vaccine within 28 days prior to randomization

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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500 participants in 2 patient groups

Arm A (Pirtobrutinib)

Experimental group

Description:

Orally

Treatment:

Drug: Pirtobrutinib

Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib)

Active Comparator group

Description:

Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.

Treatment:

Drug: Zanubrutinib

Drug: Acalabrutinib

Drug: Ibrutinib