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

• ClinicalTrials.gov Identifier: NCT04662255
• Recruitment Status: Not yet recruiting
• First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Sponsor: Loxo Oncology, Inc.
• Information provided by (Responsible Party): Loxo Oncology, Inc.

Study Description

Brief Summary:

This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare 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.

Condition or disease	Intervention/treatment	Phase
Lymphoma, Mantle-Cell	Drug: LOXO-305; Drug: Ibrutinib; Drug: Acalabrutinib; Drug: Zanubrutinib	Phase 3

Detailed Description:

This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
• Estimated Study Start Date: January 2021
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: February 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A (LOXO-305); Orally	Drug: LOXO-305; Oral LOXO-305
Active Comparator: Arm B (ibrutinib, acalabrutinib, or zanubrutinib); Orally	Drug: Ibrutinib; Oral; Other Name: Imbruvica; Drug: Acalabrutinib; Oral; Other Name: Calquence; Drug: Zanubrutinib; Oral; Other Name: Brukinsa

Outcome Measures

Primary Outcome Measures :

1. To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL) [ Time Frame: Up to approximately 24 months ]
   Assessed per Lugano criteria

Secondary Outcome Measures :

1. To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: Up to approximately 24 months ]
   Defined as the time from randomization to progressive disease (PD) or start of new treatment for MCL or withdrawal from trial due to toxicity or death
2. To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: Up to approximately 24 months ]
   Time from randomization to time when discontinuation criteria met
3. Time to worsening (TTW) of MCL-related symptoms [ Time Frame: Up to approximately 24 months ]
   Using symptom questions identified from the European Organization for Research and Treatment of Cancer (EORTC) item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.
4. Comparative Tolerability as measured by proportion of time with high side effect burden [ Time Frame: Up to approximately 24 months ]
   Using 18 items covering 10 Patient Reported Outcome- Common Terminology Criteria for Adverse Events (PRO-CTCAE) concepts for frequency (0-5 with 5 as most frequent), and/or presence (0-1 with 1 being present), or Severity (0-5 with 5 as most severe) and/or presence (0-1 with 1 being present); these selective adverse events will be framed and then overall side effect burden will be ascertained with the Functional Assessment of Cancer Therapy (FACT) - Item GP5. The range of this item is 0 -4 with 4 as most bothersome.
5. To compare Overall Response Rate (ORR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: Up to approximately 24 months ]
   Assessed per Lugano criteria
6. To compare Duration of Response (DOR) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: Up to approximately 24 months ]
   Assessed per Lugano criteria
7. To compare Overall Survival of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms [ Time Frame: Up to approximately 24 months ]
   Assessed by survival

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption
• Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
• Vaccination with live vaccine within 28 days prior to randomization

Contacts and Locations

Contacts

Contact: Patient Advocacy; 1-855-LOXO-305; clinicaltrials@loxooncology.com

Sponsors and Collaborators

Loxo Oncology, Inc.

Investigators

• Study Director: Jennifer Kherani, MD; Loxo Oncology

More Information

• Responsible Party: Loxo Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT04662255
• Other Study ID Numbers: LOXO-BTK-20019
• First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Loxo Oncology, Inc.:

Bruton's Tyrosine Kinase Inhibitor; BTKi; Hematologic Disease; Lymphoma, non-Hodgkin's; Lymphoma, B-Cell; Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Mantle-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Zanubrutinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action