A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
BRUIN-CLL-314
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)
4 other identifiers
interventional
662
22 countries
141
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2022
Longer than P75 for phase_3
141 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 15, 2022
CompletedFirst Posted
Study publicly available on registry
February 24, 2022
CompletedStudy Start
First participant enrolled
July 22, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 10, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2028
ExpectedApril 20, 2026
April 1, 2026
2.9 years
February 15, 2022
April 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
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
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
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 Outcomes (9)
IRC-assessed Progression-Free Survival (PFS)
Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)
Investigator assessed Progression-Free Survival (PFS)
Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)
Event-Free Survival (EFS)
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 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)
Randomization to death from any cause (approximately 6 years)
- +4 more secondary outcomes
Study Arms (3)
Pirtobrutinib Part 1
EXPERIMENTALParticipants will receive pirtobrutinib orally.
Ibrutinib
ACTIVE COMPARATORParticipants will receive ibrutinib orally.
Pirtobrutinib Part 2
EXPERIMENTALParticipants will receive pirtobrutinib orally.
Interventions
Administered orally.
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (144)
Pacific Cancer Medical Center, Inc
Anaheim, California, 92801, United States
TOI Clinical Research
Cerritos, California, 90703, United States
Stanford School of Medicine-Cancer Clinical Trials Office
Palo Alto, California, 94305, United States
California Cancer Associates for Research and Excellence
San Marcos, California, 92069, United States
Florida Cancer Specialists
Fort Myers, Florida, 33916-2233, United States
Cancer Specialists of North Florida -St Augustine
Saint Augustine, Florida, 32086, United States
Florida Cancer Specialists East
West Palm Beach, Florida, 33401, United States
Hematology Oncology Clinic
Baton Rouge, Louisiana, 70809, United States
Tulane Cancer Center Office of Clinical Research
New Orleans, Louisiana, 70112, United States
American Oncology Partners of Maryland, PA
Bethesda, Maryland, 20817, United States
St. Vincent Frontier Cancer Center
Billings, Montana, 59102, United States
Cancer Care Associates of York
York, Pennsylvania, 17403, United States
Prisma Health Cancer Institute
Greenville, South Carolina, 29605, United States
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203, United States
Kelsey Research Foundation
Houston, Texas, 77025, United States
Lumi Research
Kingwood, Texas, 77339, United States
Virginia Cancer Institute
Richmond, Virginia, 23230, United States
Medical Oncology Associates, PS
Spokane, Washington, 99208, United States
MultiCare Health System Institute for Research and Innovation
Spokane, Washington, 99218, United States
Alexander Fleming
Ciudad Autónoma de Buenos Aire, C1426ANZ, Argentina
Hospital Privado De Comunidad
Mar del Plata, 7600, Argentina
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares
Santa Fe, 3000, Argentina
One Clinical Research
Nedlands, 6009, Australia
Western Health, Sunshine Hospital
St Albans, 3021, Australia
The Perth Blood Institute
West Perth, 6005, Australia
Hanusch Krankenhaus
Vienna, 1140, Austria
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, 3000, Belgium
VITAZ
Sint-Niklaas, B-9100, Belgium
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, 14784400, Brazil
Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
Botucatu, 18618-687, Brazil
Hemocentro Unicamp
Campinas, 13083-878, Brazil
Hospital Uopeccan - Centro de Pesquisa Clinica
Cascavel, 85806-300, Brazil
Centro Integrado de Oncologia de Curitiba
Curitiba, 80810050, Brazil
Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer
Curitiba, 81520060, Brazil
Instituto do Câncer - Hospital São Vicente de Paulo
Passo Fundo, 99010090, Brazil
Centro Gaucho Integrado - Mae de Deus Center
Porto Alegre, 90110270, Brazil
Hospital de Clínicas de Ribeirão Preto
Ribeirão Preto, 14051-140, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
Santo André, 09060-650, Brazil
Centro Integrado de Pesquisa Clinica
São José do Rio Preto, 15090-000, Brazil
Hospital BP
São Paulo, 01321-001, Brazil
Hospital da Clinicas da Faculdade de Medicina da USP
São Paulo, 05403-000, Brazil
Hospital Santa Marcelina
São Paulo, 08270-120, Brazil
Royal Victoria Hospital-Montreal
Montreal, H3A 1A1, Canada
Hopital de L'Enfant Jesus
Québec, G1J 1Z4, Canada
Cancer Care Manitoba
Winnipeg, R3E 0V9, Canada
Inmunocel
Santiago, 7580206, Chile
CeCim Biocinetic
Santiago, 8320000, Chile
Sociedad de Investigaciones Médicas Limitada
Temuco, 4780000, Chile
Centro de Investigaciones Clínicas Viña del Mar (CIC)
Viña del Mar, 2520000, Chile
The Second Xiangya Hospital of Central South University
Changsha, 410011, China
Hunan Cancer Hospital
Changsha, 410013, China
Sun Yat-sen University Cancer Center
Guangzhou, 510060, China
Southern Medical University Nanfang Hospital
Guangzhou, 510515, China
Hainan General Hospital
Haikou, 570311, China
First Affiliated Hosp of College of Med, Zhejiang University
Hangzhou, 310003, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, 310009, China
Anhui Provincial Hospital
Hefei, 230001, China
The Second Hospital of Anhui Medical University
Hefei, 231200, China
Jiangxi Provincial Cancer Hospital
Nanchang, 330029, China
Guangxi Medical University Affiliated Tumor Hospital
Nanning, 530021, China
Fudan University Shanghai Cancer Center
Shanghai, 200032, China
Blood Institute of the Chinese Academy of Medical science
Tianjin, 300020, China
Tianjin Medical University General Hospital
Tianjin, 300052, China
Affiliated Cancer Hospital of Xinjiang Medical University
Ürümqi, 830000, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430022, China
Wu Han Tongji Hospital
Wuhan, 430030, China
The Fourth Affiliated Hospital Zhejiang University School of Medicine
Yiwu, 322000, China
Fakultni nemocnice Brno
Brno, 62500, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Fakultni Nemocnice Ostrava
Ostrava, 708 52, Czechia
Fakultni Nemocnice Plzen
Pilsen, 305 99, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, 10034, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 12808, Czechia
CHD Vendee
La Roche-sur-Yon, 85000, France
Centre Hospitalier du Mans
Le Mans, 72000, France
Centre Hospitalier Universitaire (Limoges) (CHU DUPUYTREN 1)
Limoges, 87042, France
CHU de Nantes - Hotel Dieu
Nantes, 44093, France
Centre Antoine Lacassagne
Nice, 06189, France
Hopital de la Pitie Salpetriere
Paris, 75651, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495, France
Hôpital de Pontchaillou
Rennes, 35033, France
Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen
Rouen, 76038, France
CHRU De Tours
Tours, 37044, France
Gemeinschaftspraxis für Hämatologie und Onkologie (Gefos)
Dortmund, 44309, Germany
Onkologische Gemeinschaftspraxis / BAG
Dresden, 01307, Germany
Universitaetsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik 1
Dresden, 01307, Germany
Universitätsklinikum Ulm
Ulm, 89075, Germany
Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum
Debrecen, 4004, Hungary
Markusovszky Egyetemi Oktatokorhaz
Szombathely, 9700, Hungary
Hadassah Medical Center
Jerusalem, 9112001, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
Alessandria, 15100, Italy
Policlinico Sant'Orsola Malpighi
Bologna, 40138, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014, Italy
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Azienda Unita Sanitaria Locale di Reggio Emilia
Reggio Emilia, 42122, Italy
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
Yamagata University Hospital
Yamagata, 990-9585, Japan
Dunedin Hospital
Dunedin, 9016, New Zealand
Waikato Hospital
Hamilton, 3204, New Zealand
Momentum Clinical Research
Newtown, 6242, New Zealand
Middlemore Clinical Trials
Papatoetoe, 2025, New Zealand
KO-MED Centra Kliniczne
Biała Podlaska, 21500, Poland
Szpital Uniwersytecki nr 1 im. Antoniego Jurasza
Bydgoszcz, 85-168, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
Pratia Onkologia Katowice
Katowice, 40519, Poland
Pratia MCM Krakow
Krakow, 30-510, Poland
Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1
Lublin, 20-081, Poland
AIDPORT Sp. z o.o.
Skórzewo, 60-185, Poland
Uniwersytecki Szpital Kliniczny Klinika
Wroclaw, 50-367, Poland
Inje Univ Busan Paik Hospital
Busan, 47392, South Korea
The Catholic University of Korea-Seoul St. Mary's Hospital
Seocho-Gu, 06591, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hospital de la Santa Creu i Sant Pau
Barcelona, 08025, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 8035, Spain
Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908, Spain
Hospital Universitario Infanta Leonor-INTERNAL MED
Madrid, 28031, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, 28222, Spain
Hospital Costa Del Sol
Marbella, 29600, Spain
Clinica Universitaria De Navarra
Pamplona, 31008, Spain
Hospital De Navarra
Pamplona, 31008, Spain
Hospital Universitario Marqués de Valdecilla
Santander, 39008, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Chang Bing Show Chwan Memorial Hospital
Changhua, 710, Taiwan
Chang Gung Memorial Hospital - Chiayi
Chiayi County, 61363, Taiwan
National Cheng-Kung Uni. Hosp.
Tainan, 704, Taiwan
Koo Foundation Sun Yan-Sen Cancer Center
Taipei, 112, Taiwan
Gazi University Faculty of Medicine
Ankara, 6500, Turkey (Türkiye)
9 Eylul University Hospital
Balçova, 35100, Turkey (Türkiye)
Ege Üniversitesi
Bornova, 35040, Turkey (Türkiye)
Istanbul University Istanbul Medicine Faculty
Faith, 34732, Turkey (Türkiye)
American Hospital
Istanbul, 34365, Turkey (Türkiye)
Acıbadem Maslak Hastanesi
Istanbul, 34457, Turkey (Türkiye)
Ankara University Medicine Hospital
Mamak, 06590, Turkey (Türkiye)
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Castle Hill Hospital
Cottingham, HU16 5JQ, United Kingdom
HOPE Centre
Leicester, LE1 5WW, United Kingdom
St Bartholomew's Hospital
London, EC1A 7BE, United Kingdom
Singleton Hospital
Swansea, SA2 8QA, United Kingdom
Related Publications (2)
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: 41749915DERIVEDWoyach 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/Small Lymphocytic Lymphoma. J Clin Oncol. 2026 Feb 20;44(6):476-485. doi: 10.1200/JCO-25-02477. Epub 2025 Dec 7.
PMID: 41353787DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Central Study Contacts
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACT
Physicians interested in becoming principal investigators please contact
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
February 15, 2022
First Posted
February 24, 2022
Study Start
July 22, 2022
Primary Completion
June 10, 2025
Study Completion (Estimated)
January 1, 2028
Last Updated
April 20, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.