A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (BRUIN CLL-322)

January 27, 2026 updated by: Loxo Oncology, Inc.

A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-322)

The purpose of this study is to compare the efficacy and safety of fixed duration pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with CLL/SLL who have been previously treated with at least one prior line of therapy. Participation could last up to five years.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Royal Adelaide Hospital
      • Frankston, Australia, 3199
        • Peninsula Private Hospital
      • Hobart, Australia, 7000
        • Royal Hobart Hospital
      • Melbourne, Australia, 3004
        • The Alfred Hospital
      • Melbourne, Australia, 3065
        • St Vincent's Hospital
      • Perth, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Belgium
      • Ghent, Belgium, 9000
        • Universitair Ziekenhuis Gent
      • La Louvière, Belgium, 7100
        • Groupe Jolimont
      • Yvoir, Belgium, 5530
        • CHU UCL Namur Site Godinne
  • Canada
      • Calgary, Canada, T2N 2T9
        • Foothills Medical Centre
      • Edmonton, Canada, T6G 1Z2
        • Cross Cancer Institute
      • Montreal, Canada, H3T 1E2
        • Jewish General Hospital
      • Toronto, Canada, M4N 3M5
        • Sunnybrook Research Institute
      • Vancouver, Canada, V5Z 4E6
        • BC Cancer Vancouver
      • Winnipeg, Canada, R3A 1M3
        • Cancer Care Manitoba
  • China
      • Beijing, China, 100044
        • Peking University People's Hospital
      • Beijing, China, 100034
        • Peking University First Hospital
      • Changsha, China, 410008
        • The Second Xiangya Hospital of Central South University
      • Chongqing, China, 400030
        • Chongqing Cancer Hospital
      • Fuzhou, China, 350014
        • Fujian Provincial Cancer Hospial
      • Guangzhou, China, 510000
        • Cancer Center of Guangzhou Medical University
      • Hangzhou, China, 310003
        • First Affiliated Hosp of College of Med, Zhejiang University
      • Hefei, China, 230022
        • The First Affiliated Hospital of Anhui Medical University
      • Hengyang, China, 421001
        • The First Affiliated Hospital of University of South China
      • Hohhot, China, 010050
        • The Affiliated Hospital of Inner Mongolia Medical University
      • Kunming, China, 650034
        • The First People's Hospital of Yunnan Province
      • Nanchang, China, 330029
        • Jiangxi Provincial Cancer Hospital
      • Nanjing, China, 210029
        • Jiangsu Province Hospital
      • Nanning, China, 530021
        • Guangxi Medical University Affiliated Tumor Hospital
      • Nantong, China, 226000
        • Nantong Tumor Hospital
      • Qingdao, China, 266555
        • The Affiliated Hospital Of Qingdao University
      • Shanghai, China, 200025
        • Shanghai Jiaotong University School of Medicine Ruijin Hospital
      • Shanghai, China, 200336
        • Shanghai Tongren Hospital
      • Shenyang, China, 110004
        • Shengjing Hospital Of China Medical University
      • Tianjin, China, 300060
        • Tianjin Medical University Cancer Institute and Hospital
      • Wuhan, China, 430022
        • Wuhan Union Hospital
      • Wuhan, China, 430030
        • Wu Han Tongji Hospital
      • Wuxi, China, 214023
        • Wuxi People's Hospital
      • Yichang, China, 443003
        • Yichang Central People's Hospital
      • Zhengzhou, China, 450003
        • Henan Provincial People's Hospital
      • Zhengzhou, China, 450008
        • Henan Cancer Hospital
      • Zhongshan, China, 528403
        • Zhongshan City People's Hospital
  • Czechia
      • Brno, Czechia, 62500
        • Fakultni Nemocnice Brno
      • Hradec Králové, Czechia, 500 05
        • Fakultni nemocnice Hradec Kralove
      • Prague, Czechia, 12808
        • Vseobecna fakultni nemocnice v Praze
      • Prague, Czechia, 10034
        • Fakultni nemocnice Kralovske Vinohrady
  • Denmark
      • Copenhagen, Denmark, 2200
        • Rigshospitalet
  • France
      • Le Mans, France, 72000
        • Centre Hospitalier du Mans
      • Montpellier, France, 34295
        • Hopital Saint Eloi
      • Morvan, France, 54511
        • Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois
      • Nantes, France, 44093
        • CHU de Nantes - Hotel Dieu
      • Paris, France, 75010
        • Hopital Saint Louis
      • Paris, France, 75651
        • Hôpital de la Pitié Salpêtrière
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier Lyon Sud
      • Politiers, France, 86021
        • Pole Regionalde Cancérologie(CHU de Poitiers)
      • Rennes, France, 35033
        • Hôpital de Pontchaillou
      • Rouen, France, 76038
        • Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen
      • Strasbourg, France, 67033
        • ICANS_Institut de Cancerologie Strasbourg Europe
      • Tours, France, 37044
        • Chru de Tours
  • Germany
      • Chemnitz, Germany, 09131
        • Klinikum Chemnitz GmbH
      • Essen, Germany, 45147
        • Universtitätsklinikum Essen AöR
      • Kerpener, Germany, 50937
        • Uniklinik Köln
      • Koelner Platz 1, Germany, 80804
        • München Klinik Schwabing
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig AöR Klinik und Poliklinik für Hämatologie
      • Rostock, Germany, 18057
        • Unimedizin RostockZIM III -Haemtologie
      • Würzburg, Germany, 97080
        • Gemeinschaftspraxis Dres. Schöttker & Pretscher, z.Hd. Sophie Enz
  • Hungary
      • Budapest, Hungary, 1122
        • National Institute of Oncology
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont
  • Ireland
      • Dublin, Ireland
        • Mater Misericordiae Hospital
      • Waterford, Ireland, X91 ER8E
        • University Hospital Waterford
  • Israel
      • Haifa, Israel, 3339419
        • Bnai Zion Medical Center
      • Nahariya, Israel, 22100
        • Galilee Medical Center
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center
      • Rehovot, Israel, 7610001
        • Kaplan Medical Center
      • Tel Aviv, Israel, 6423906
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Bologna, Italy, 40138
        • IRCCS - AOU di Bologna
      • Catanzaro, Italy, 88100
        • Azienda Ospedaliera Pugliese Ciaccio
      • Cona, Italy, 44124
        • AOU Arcispedale Sant'Anna
      • Cuneo, Italy, 12100
        • Ospedale Santa Croce e Carle
      • Florence, Italy, 50134
        • Azienda Ospedaliera Universitaria Careggi
      • Meldola, Italy, 47014
        • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
      • Milan, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Milan, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C
      • Modena, Italy, 41224
        • A.O.U. di Modena
      • Novara, Italy, 28100
        • Azienda Ospedale Maggiore Della Carita
      • Roma, Italy, 00168
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Universita Cattolica del Sacro Cuore
      • Rome, Italy, 00161
        • Policlinico Umberto I - Haematology
      • Torino, Italy, 10126
        • A.O.U. Citta' della Salute e della Scienza di Torino
  • Japan
      • Bunkyō City, Japan, 113-8519
        • Tokyo Medical and Dental University Hospital
      • Chiba-Ken, Japan, 277 8577
        • National Cancer Center Hospital East
      • Chūō, Japan, 409-3821
        • University of Yamanashi Hospital
      • Chūōku, Japan, 104-0045
        • National Cancer Center Hospital
      • Fukui, Japan, 9101193
        • University of Fukui Hospital
      • Kyoto, Japan, 602-8566
        • Kyoto Furitsu Medical University Hospital
      • Kōtō City, Japan, 135-8550
        • Japanese Foundation for Cancer Research
      • Nankoku, Japan, 783-8505
        • Kochi Medical School Hospital
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 534-0021
        • Osaka City General Hospital
  • Norway
      • Nordbyhagen, Norway, 1474
        • Akershus Universitetssykehus
      • Trondheim, Norway, 7006
        • St-Olavs Hospital
  • Poland
      • Gdynia, Poland, 81-519
        • Szpitale Pomorskie Sp. z o. o.
      • Katowice, Poland, 40519
        • Pratia Onkologia Katowice
      • Krakow, Poland, 30-510
        • Pratia McM Krakow
      • Lodz, Poland, 93510
        • Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii
      • Lublin, Poland, 20-081
        • Klinika Hematoonkologii i Transplantacji Szpiku,Samodzielny Publiczny Szpital Kliniczny Nr 1
      • Torun, Poland, 87-100
        • MICS Centrum Medyczne Torun
      • Warsaw, Poland
        • Instytut Hermatologii I Transfuzjologii
  • Singapore
      • Singapore, Singapore, 169078
        • Singapore General Hospital
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 8035
        • Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 8041
        • Hospital De La Santa Creu I Sant Pau
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jimenez Díaz
      • Madrid, Spain, 28031
        • Hospital Universitario Infanta Leonor
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Majadahonda, Spain, 28222
        • Hospital Puerta de Hierro
      • Marbella, Spain, 29600
        • Hospital Costa Del Sol
      • Oviedo, Spain, 33011
        • Hospital Universitario Central de Asturias
      • Pozuelo de Alarcón, Spain, 28223
        • Hospital Universitario Quironsalud Madrid
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Seville, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Toledo, Spain, 45007
        • Hospital Universitario de Toledo
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe
  • Sweden
      • Lund, Sweden, 22185
        • Skanes Universitetssjukhus, Hematoloaimottagningen
      • Stockholm, Sweden, 17176
        • Karolinska Universitetssjukhuset i Solna
  • Switzerland
      • Bellinzona, Switzerland, 6500
        • Ospedale Regionale Bellinzona e Valli
      • Lucerne, Switzerland, 6000
        • Luzerner Kantonsspital
  • Taiwan
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • Leeds, United Kingdom, LS9 7TF
        • St James's University Hospital
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital
      • Oxford, United Kingdom, OX3 7LJ
        • Churchill Hospital
      • Plymouth, United Kingdom, PL6 8DH
        • Derriford Hospital
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Ironwood Physicians, Ironwood Cancer and Research Centers
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital
    • California
      • Orange, California, United States, 92868
        • University of California Irvine Medical Center
      • San Diego, California, United States, 92111
        • Scripps Mercy Hospital
      • Santa Rosa, California, United States, 95403
        • Providence Medical Foundation
    • Connecticut
      • Stamford, Connecticut, United States, 06902
        • Stamford Hospital
    • Florida
      • Fort Myers, Florida, United States, 33916-2233
        • Florida Cancer Specialists
      • Saint Augustine, Florida, United States, 32086
        • Cancer Specialists of North Florida -St Augustine
      • West Palm Beach, Florida, United States, 33401
        • Florida Cancer Specialists East
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Mission Cancer and Blood
    • Kentucky
      • Pikeville, Kentucky, United States, 41501
        • Pikeville Medical Center, Inc.
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • American Oncology Partners of Maryland, PA
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Ann Arbor, Michigan, United States, 48106
        • St. Joseph Mercy Hospital
    • Minnesota
      • Rochester, Minnesota, United States, 55905-0002
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center at Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10029
        • The Mount Sinai Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28204
        • Novant Cancer Institute Charlotte
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Wilson, North Carolina, United States, 27893
        • Regional Medical Oncology Center
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care Inc
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43210
        • The James Cancer Hospital
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Oncology Associates of Bridgeport P.C.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SCRI
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78240
        • USO - Texas Oncology - San Antonio
    • Virginia
      • Charlottesville, Virginia, United States, 22908-0816
        • University of Virginia Health System
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC - Lee Highway
      • Richmond, Virginia, United States, 23298-0070
        • Virginia Commonwealth University Massey Cancer Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute; STE 1020
      • Seattle, Washington, United States, 98104-2092
        • Fred Hutchinson Cancer Research Center
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
  • Previous treatment with at least one line of therapy that may include a covalent Bruton's tyrosine kinase (BTK) inhibitor
  • Platelets greater than or equal to (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL) and absolute neutrophil count ≥1.0 x 10⁹/L
  • Adequate organ function
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

Exclusion Criteria:

  • Known or suspected Richter's transformation at any time preceding enrollment
  • Prior therapy with a non-covalent (reversible) BTK inhibitor
  • Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
  • Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers
  • Prior therapy with venetoclax
  • Central nervous system (CNS) involvement
  • Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
  • Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
  • Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within 60 days
  • Active hepatitis B or hepatitis C
  • Known active cytomegalovirus (CMV) infection
  • Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia (AIHA)
  • Significant cardiovascular disease
  • Vaccination with a live vaccine within 28 days prior to randomization

  • Patients with the following hypersensitivity:

    • Known hypersensitivity to any component or excipient of pirtobrutinib and venetoclax
    • Prior significant hypersensitivity to rituximab
    • Known allergy to allopurinol and inability to take uric acid lowering agent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A (PVR)
Fixed duration pirtobrutinib in combination with venetoclax and rituximab
Drug: Pirtobrutinib
Oral
Other Names:
  • LOXO-305
  • LY3527727
Drug: Venetoclax
Oral
Other Names:
  • Venclexta
  • Venclyxto
Drug: Rituximab
Intravenous (IV)
Other Names:
  • Rituxan
  • MabThera
  • Riabni
  • Ruxience
  • Truxima
Active Comparator: Arm B (VR)
Venetoclax with rituximab
Drug: Venetoclax
Oral
Other Names:
  • Venclexta
  • Venclyxto
Drug: Rituximab
Intravenous (IV)
Other Names:
  • Rituxan
  • MabThera
  • Riabni
  • Ruxience
  • Truxima

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loxo Oncology, Inc.

Collaborators

Eli Lilly and Company

Investigators

  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2021

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

July 15, 2021

First Submitted That Met QC Criteria

July 15, 2021

First Posted (Actual)

July 16, 2021

Study Record Updates

Last Update Posted (Actual)

January 29, 2026

Last Update Submitted That Met QC Criteria

January 27, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18087
  • LOXO-BTK-20022 (Other Identifier: Eli Lilly and Company)
  • J2N-OX-JZNO (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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