A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Purpose

The purpose of Part 1 of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL; participants may or may not have already had treatment for their cancer. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL/SLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.

Conditions

  • Chronic Lymphocytic Leukemia
  • Leukemia, Lymphocytic
  • Leukemia, B-cell
  • Small Lymphocytic Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria - Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Adequate organ function - Platelets greater than or equal to ≥ 50 x 10⁹/liter (L) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis, - Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis - Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis - Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria

  • Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment - Known or suspected central nervous system (CNS) involvement - A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease - Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) - Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter - Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests - Active cytomegalovirus (CMV) infection - Active uncontrolled systemic bacterial, viral, or fungal infection - Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count - Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments - Ongoing inflammatory bowel disease - Previous treatment for CLL/SLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent). Part 2: participants must be treatment naïve - Concurrent use of investigational agent or anticancer therapy except hormonal therapy - Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist - Use of > 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug - Vaccination with a live vaccine within 28 days prior to randomization - Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment - Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pirtobrutinib Part 1 		Participants will receive pirtobrutinib orally.
  • Drug: Pirtobrutinib
    Administered orally.
    Other names:
    • LOXO-305
    • LY3527727
Active Comparator
Ibrutinib Part 1 		Participants will receive ibrutinib orally.
  • Drug: Ibrutinib
    Administered orally.
Experimental
Pirtobrutinib Part 2 		Participants will receive pirtobrutinib orally.
  • Drug: Pirtobrutinib
    Administered orally.
    Other names:
    • LOXO-305
    • LY3527727

Recruiting Locations

Pacific Cancer Medical Center, Inc
Anaheim, California 92801
Contact:
714-999-1465

TOI Clinical Research
Cerritos, California 90703
Contact:
562-693-4477

Stanford School of Medicine-Cancer Clinical Trials Office
Palo Alto, California 94305
Contact:
650-498-6000

Florida Cancer Specialists
Fort Myers, Florida 33916-2233
Contact:
727-216-1143

Cancer Specialists of North Florida -St Augustine
Saint Augustine, Florida 32086
Contact:
904-538-4488

Florida Cancer Specialists East
West Palm Beach, Florida 33401
Contact:
561-366-4100

American Oncology Partners of Maryland, PA
Bethesda, Maryland 20817
Contact:
301-571-0019

St. Vincent Frontier Cancer Center
Billings, Montana 59102
Contact:
406-238-6685

Sarah Cannon Research Institute SCRI
Nashville, Tennessee 37203
Contact:
423-622-6212

Lumi Research
Kingwood, Texas 77339

Virginia Cancer Institute
Richmond, Virginia 23230
Contact:
804-287-3000

Medical Oncology Associates, PS
Spokane, Washington 99208
Contact:
509-462-2273

More Details

Status
Recruiting
Sponsor
Loxo Oncology, Inc.

Study Contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
LillyTrials@Lilly.com