A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.

Official Title
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A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Pirtobrutinib
* Drug: Bendamustine
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Adequate organ function Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min) Exclusion Criteria: Known or suspected Richter's transformation at any time preceding enrollment Prior systemic therapy for CLL/SLL Presence of 17p deletion Central nervous system (CNS) involvement Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) Significant cardiovascular disease Active hepatitis B or hepatitis C Active cytomegalovirus (CMV) infection Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count Concurrent use of investigational agent or anticancer therapy except hormonal therapy Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist Vaccination with a live vaccine within 28 days prior to randomization Patients with the following hypersensitivity: Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine Prior significant hypersensitivity to rituximab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients will be randomized 1:1 into Arm A and Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Pirtobrutinib)<br>Pirtobrutinib administered orally | Drug: Pirtobrutinib<br>* Oral<br>* Other names: LY3527727;|
| Active Comparator: Arm B (BR)<br>Bendamustine plus rituximab administered intravenously (IV) | Drug: Bendamustine<br>* IV<br>* Other names: Levact;Drug: Rituximab<br>* IV<br>* Other names: Ruxience;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate progression-free survival (PFS) of pirtobrutinib (Arm A) compared to bendamustine and rituximab (Arm B) | Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Response Criteria | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effectiveness of Arm A compared to Arm B: Progression-free survival (PFS) | Assessments of effectiveness include PFS, assessed by investigator | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B: Overall survival (OS) | Assessments of effectiveness include OS, assessed by investigator | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B: Time to next treatment (TTNT) | Assessments of effectiveness include TTNT, assessed by investigator | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B: Overall response rate (ORR) | Assessments of effectiveness include ORR, assessed by investigator and IRC | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B: Duration of Response (DOR) | Assessments of effectiveness include DOR, assessed by investigator and IRC | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms | Based on time to worsening of CLL/SLL-related symptoms | Up to approximately 5 years | 
| To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning | Based on time to worsening of physical functioning | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BTKi, BTK Inhibitor, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-cell