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

Official title

A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)

Overview

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.

Interventions

• Drug Pirtobrutinib
  Administered orally.
• Drug Ibrutinib
  Administered orally.

Primary outcome measures

• Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 1 [Time frame: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest] (approximately 3 years and 5 months)]
• Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (CRi), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) Part 2 [Time frame: Baseline to best overall response the best response recorded from Cycle 1 Day 1 until data cutoff date, PD, or start of new anticancer treatment, whichever is the earliest (Approximately 2 years and 3 months)]

Secondary outcome measures (9)

• IRC-assessed Progression-Free Survival (PFS) [Time frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)]
• Investigator assessed Progression-Free Survival (PFS) [Time frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)]
• Event-Free Survival (EFS) [Time frame: Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years)]
• Duration of Response (DOR) [Time frame: Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years)]
• Overall Survival (OS) [Time frame: Randomization to death from any cause (approximately 6 years)]
• Time to Next Treatment (TTNT) [Time frame: Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years)]
• Time to Worsening (TTW) of CLL/SLL Related Symptoms [Time frame: Randomization to time to worsening symptoms (approximately 4 years)]
• Comparative Tolerability [Time frame: From Baseline to Treatment Discontinuation for Any Reason (approximately 4 years)]
• Percentage of Participants Achieving DOR Part 2 [Time frame: Time from the date of the first documented response of CR, CRi, nPR, or PR to the earlier of the documentation of definitive PD or death from any cause] (Approximately 2 years)]

Eligibility criteria

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

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 · 19 centers

• Pacific Cancer Medical Center, Inc — Anaheim
• TOI Clinical Research — Cerritos
• Stanford School of Medicine-Cancer Clinical Trials Office — Palo Alto
• California Cancer Associates for Research and Excellence — San Marcos
• Florida Cancer Specialists — Fort Myers
• Cancer Specialists of North Florida -St Augustine — Saint Augustine
• Florida Cancer Specialists East — West Palm Beach
• Hematology Oncology Clinic — Baton Rouge
• … and 11 more centers

China · 18 centers

• The Second Xiangya Hospital of Central South University — Changsha
• Hunan Cancer Hospital — Changsha
• Sun Yat-sen University Cancer Center — Guangzhou
• Southern Medical University Nanfang Hospital — Guangzhou
• Hainan General Hospital — Haikou
• First Affiliated Hosp of College of Med, Zhejiang University — Hangzhou
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou
• Anhui Provincial Hospital — Hefei
• … and 10 more centers

Brazil · 14 centers

• Fundação Pio XII - Hospital de Câncer de Barretos — Barretos
• Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP — Botucatu
• Hemocentro Unicamp — Campinas
• Hospital Uopeccan - Centro de Pesquisa Clinica — Cascavel
• Centro Integrado de Oncologia de Curitiba — Curitiba
• Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer — Curitiba
• Instituto do Câncer - Hospital São Vicente de Paulo — Passo Fundo
• Centro Gaucho Integrado - Mae de Deus Center — Porto Alegre
• … and 6 more centers

Spain · 13 centers

Center list to be confirmed — check the primary protocol.

France · 10 centers

• CHD Vendee — La Roche-sur-Yon
• Centre Hospitalier du Mans — Le Mans
• Centre Hospitalier Universitaire (Limoges) (CHU DUPUYTREN 1) — Limoges
• CHU de Nantes - Hotel Dieu — Nantes
• Centre Antoine Lacassagne — Nice
• Hopital de la Pitie Salpetriere — Paris
• Centre Hospitalier Lyon Sud — Pierre-Bénite
• … and 3 more centers

Poland · 8 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 7 centers

Center list to be confirmed — check the primary protocol.

Czechia · 6 centers

• Fakultni nemocnice Brno — Brno
• Fakultni nemocnice Hradec Kralove — Hradec Králové
• Fakultni Nemocnice Ostrava — Ostrava
• Fakultni Nemocnice Plzen — Pilsen
• Fakultni nemocnice Kralovske Vinohrady — Prague
• Vseobecna fakultni nemocnice v Praze — Prague

Italy · 6 centers

Center list to be confirmed — check the primary protocol.

Chile · 4 centers

• Inmunocel — Santiago
• CeCim Biocinetic — Santiago
• Sociedad de Investigaciones Médicas Limitada — Temuco
• Centro de Investigaciones Clínicas Viña del Mar (CIC) — Viña del Mar

Germany · 4 centers

Center list to be confirmed — check the primary protocol.

New Zealand · 4 centers

Center list to be confirmed — check the primary protocol.

South Korea · 4 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 4 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

Argentina · 3 centers

• Alexander Fleming — Ciudad Autónoma de Buenos Aire
• Hospital Privado De Comunidad — Mar del Plata
• Clínica de Nefrología, Urología y Enfermedades Cardiovasculares — Santa Fe

Australia · 3 centers

• One Clinical Research — Nedlands
• Western Health, Sunshine Hospital — St Albans
• The Perth Blood Institute — West Perth

Canada · 3 centers

• Royal Victoria Hospital-Montreal — Montreal
• Hopital de L'Enfant Jesus — Québec
• Cancer Care Manitoba — Winnipeg

Belgium · 2 centers

• Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg — Leuven
• VITAZ — Sint-Niklaas

Hungary · 2 centers

Center list to be confirmed — check the primary protocol.

Israel · 2 centers

Center list to be confirmed — check the primary protocol.

Japan · 2 centers

Center list to be confirmed — check the primary protocol.

Austria · 1 center

• Hanusch Krankenhaus — Vienna

Publications

• Eyre TA, Hess LM, Masoudi E, Jen MH, Abhyankar S, Graham-Clarke PL, Bhandari NR, Maguire P, Winfree KB, Tracey M, Taipale KL, Davids MS. Efficacy of Pirtobrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2026 Feb 18;18(4):660. doi: 10.3390/cancers18040660. PMID 41749915
• Woyach JA, Qiu L, Grosicki S, Wrobel T, Capra M, Czyz J, Yi S, Eom KS, Panovska A, Jurczak W, Laribi K, Jacobasch L, Baker R, Agajanian R, Berkovits A, Ozcan M, Lepretre S, Coombs CC, Cramer P, Lewis KL, Hill M, Bao K, Bian Y, De Batista Ribeiro SR, Bhandari NR, Ruppert AS, Leow CC, Wierda WG. Pirtobrutinib Versus Ibrutinib in Treatment-Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Sm PMID 41353787

Identifiers

NCT: NCT05254743 · 18281 · J2N-OX-JZNU · LOXO-BTK-20030 · 2023-507699-38-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗