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Chronic Lymphocytic LeukemiaPhase 1/2NCT03740529

A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

A Phase 1/2 study testing Pirtobrutinib, Venetoclax and Rituximab in people with Chronic Lymphocytic Leukemia and Waldenstrom Macroglobulinemia, run by Loxo Oncology, Inc. at 56 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 (pirtobrutinib) in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pirtobrutinib, Venetoclax and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
803 participants
Where
56 sitesin 10 countries
Study dates
15 Mar 2019to 23 Dec 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed CLL/SLL, WM, or NHL intolerant to either ≥ 2 prior standard of care regimens given in combination or sequentially OR have received 1 prior BTK inhibitor-containing regimen when a BTK inhibitor is approved as first line therapy (Phase 1) OR with prior treatment defined by phase 2 cohort (Phase 2 Patients only).
  • Adequate hematologic function (Phase 1 and 1b Patients only).
  • Responsive to transfusion support if given for thrombocytopenia or anemia (Phase 1 and 1b Patients only).
  • Histologically confirmed relapsed/recurrent CLL in whom venetoclax is appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm A Patients only).
  • Histologically confirmed relapsed/refractory CLL in whom venetoclax + rituximab is appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm B Patients only).
  • Eastern Cooperative Oncology Group (ECOG) 0-2.
Show all 9Show fewer
  • Adequate hepatic and renal function.
  • Ability to receive study drug therapy orally.
  • Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal [and 2 years of non-therapy-induced amenorrhea] or surgically sterile) to observe conventional and effective birth control.

Who cannot join

  • Investigational agent or anticancer therapy within 5 half-lives or 14 days, whichever is shorter, prior to planned start of specified study therapy except antineoplastic and immunosuppressant monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of pirtobrutinib. In addition, no concurrent systemic anticancer therapy is permitted.
  • Major surgery within 4 weeks prior to planned start of specified study therapy.
  • Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment.
  • Pregnancy or lactation.
  • Patients requiring therapeutic anticoagulation with warfarin.
  • Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 or greater at the time of starting study treatment except for alopecia.
Show all 20Show fewer
  • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 60 days (180 days before the PK trigger) prior to planned start of specified study therapy.
  • Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible and enrolled to phase 2 Cohort 7 if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval.
  • Active uncontrolled auto-immune cytopenia where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts.
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of pirtobrutinib.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
  • Patients who have tested positive for human immunodeficiency virus (HIV) are excluded. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for enrollment.
  • Clinically significant active malabsorption syndrome.
  • Current treatment with certain strong CYP3A4 inhibitors or inducers and/or strong P-gp inhibitors.
  • For patients enrolled to phase 1b Arm A or B: Patients with prior treatment with venetoclax or other BCL-2 inhibitors.
  • Prior treatment with pirtobrutinib.
  • Active second malignancy unless in remission and with life expectancy > 2 years.
  • Known hypersensitivity to any component or excipient of pirtobrutinib.
  • For patients enrolled to phase 1b Arm B: Patients with prior significant hypersensitivity, allergy, or anaphylactic reaction to rituximab/biosimilar requiring discontinuation.
  • Patients with prior significant hypersensitivity to rituximab requiring discontinuation, prior allergic or anaphylactic reaction to rituximab (Phase 1b Arm B Patients only).

Trial locations and contacts

56 sites in 10 countries.

56 sites in 10 countries

United States31 sites

  • Emory Clinic

    Atlanta, Georgia, 30322

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Hospital

    Columbus, Ohio, 43210

  • Mary Crowley Cancer Research Center

    Dallas, Texas, 75230

  • Durham VA Medical Center

    Durham, North Carolina, 27705

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Florida Cancer Specialists ORLANDO/DDU

    Lake Mary, Florida, 32746

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Sarah Cannon Research Institute SCRI

    Nashville, Tennessee, 37203

  • Smilow Cancer Hospital at Yale-New Haven

    New Haven, Connecticut, 06510

  • Northwell Health

    New Hyde Park, New York, 11042

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68105

  • University of Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota, 55905-0002

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • Scripps Coastal Medical Center

    San Diego, California, 92103

  • University of California San Francisco, Medical Center at Paranassus

    San Francisco, California, 94117

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Mayo Clinic of Scottsdale

    Scottsdale, Arizona, 85259

  • Swedish Medical Center

    Seattle, Washington, 98104

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98195

Other trials in United States

Japan10 sites

  • National Cancer Center Hospital

    Chuo Ku, Tokyo, 104-0045

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 811-1395

  • Tokai University Hospital- Isehara Campus

    Isehara, Kanagawa, 259-1193

  • Kyoto Furitsu Medical University Hospital

    Kyoto, 602-8566

  • Nagoya Medical Center

    Nagoya, Aichi-ken, 460-0001

  • Kochi Medical School Hospital

    Nankoku, Kochi, 783-8505

  • Okayama University Hospital

    Okayama, 700-8558

  • Kindai University Hospital

    Osakasayama-Shi, 589-8511

  • Hokkaido University Hospital

    Sapporo, Hokkaido, 060-8648

  • Tohoku University Hospital

    Sendai, Miyagi, 980-8574

Other trials in Japan

Australia3 sites

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Linear Clinical Research

    Nedlands, Western Australia, 6009

Other trials in Australia

United Kingdom3 sites

  • St James's University Hospital

    Leeds, LS9 7TF

  • Churchill Hospital

    Oxford, OX3 7LJ

  • Derriford Hospital

    Plymouth, Pl6 8DH

Other trials in United Kingdom

Italy2 sites

  • IRCCS - AOU di Bologna

    Bologna, 40138

  • IRCCS Ospedale San Raffaele

    Milan, 20132

Other trials in Italy

Poland2 sites

  • Pratia MCM Krakow

    Krakow, 30-510

  • Instytut Hermatologii I Transfuzjologii

    Warsaw

Other trials in Poland

South Korea2 sites

  • Samsung Medical Center

    Seoul, Seoul-teukbyeolsi [Seoul], 06351

  • Seoul National University Hospital

    Seoul, 03080

Other trials in South Korea

France1 site

  • Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu

    Nantes, 44093

Other trials in France

Sweden1 site

  • Karolinska Institutet

    Solna, AB, 171 65

Other trials in Sweden

Switzerland1 site

  • Ospedale Regionale Bellinzona e Valli

    Bellinzona, Canton Ticino, 6500

Other trials in Switzerland

About this study

Official title: A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)

This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 (pirtobrutinib) in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.

Read the detailed description

This study includes 3 parts: Phase 1 (pirtobrutinib monotherapy dose escalation and dose expansion), Phase 1b (pirtobrutinib combination therapy dose expansion), and Phase 2 (pirtobrutinib monotherapy dose expansion). In Phase 1, patients will be enrolled using an accelerated titration design. The starting dose of pirtobrutinib in oral tablet form is 25 mg/day (e.g., 25 mg once daily [QD]). Once the MTD and/or RP2D is identified in Phase 1 dose escalation, enrollment will continue to Phase 1 dose expansion and can commence to Phase 1b (Arms A and B). For Phase 2, patients will be enrolled to one of seven Phase 2 dose expansion cohorts depending on tumor histology and prior treatment history. Cycle length will be 28 days.

Being tested
Pirtobrutinib, Venetoclax, Rituximab
Keywords
Loxo, LOXO-305, BTK, Bruton's tyrosine kinase, CLL, SLL, NHL, Chronic Lymphocytic Leukemia, C481S, C481, Ibrutinib, Acalabrutinib, Zanubrutinib, BGB-3111, GS-4059, ONO-4059, Tirabrutinib, Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Waldenstrom macroglobulinemia
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Dendritic Cell Sarcoma, Interdigitating, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirtobrutinibDrug

    Also called LOXO-305, LY3527727

    Oral

  • VenetoclaxDrug

    Also called Venclexta, Venclyxto

    Oral

  • RituximabDrug

    Also called Rituxan, MabThera

    IV

Study groups in NCT03740529
Study groupRoleWhat they receive
Phase I Dose Escalation (Pirtobrutinib Monotherapy)ExperimentalDose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 3ExperimentalCLL/SLL patients with no prior therapy.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 1ExperimentalNon-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 4ExperimentalCLL/SLL patients treated with prior therapy, BTK inhibitor naïve.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 2ExperimentalCLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 5ExperimentalWM patients treated with a prior BTK inhibitor-containing regimen.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 6ExperimentalMZL patients treated with a prior BTK inhibitor-containing regimen.
Receives: Drug: Pirtobrutinib
Phase 2 (Pirtobrutinib Monotherapy) Cohort 7ExperimentalDefined as CLL/SLL or NHL not otherwise specified in Cohorts 1 through 6, inclusive of CLL/SLL, Richter's transformation, or low grade NHL with transformation, blastoid MCL, and patients with history of CNS involvement or primary CNS lymphoma. In the event the Sponsor electively closes Cohorts 2-4 prior to completion, patients with CLL/SLL who are ineligible to participate in or unable to access late phase studies of pirtobrutinib may be eligible to enroll in this cohort Diffuse large B-cell lymphoma (DLBCL) is excluded. MCL without prior BTK inhibitor treatment is excluded. Patients enrolling to Cohort 7 must have received one or more prior therapies or have no available approved therapy with demonstrated clinical benefit with the exception of untreated Richter's transformation, which is allowed.
Receives: Drug: Pirtobrutinib
Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm AExperimentalRelapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax
Receives: Drug: Pirtobrutinib; Drug: Venetoclax
Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm BExperimentalRelapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab
Receives: Drug: Pirtobrutinib; Drug: Venetoclax; Drug: Rituximab
Phase 1 Dose Expansion (Pirtobrutinib Monotherapy)ExperimentalPatients to receive the recommended Phase 2 dose of pirtobrutinib
Receives: Drug: Pirtobrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    Phase I

    Measured: Up to 24 Months

  2. Recommended dose for further study

    Phase I

    Measured: Up to 24 Months

  3. To assess the preliminary anti-tumor activity of pirtobrutinib based on ORR as assessed by an Independent Review Committee (IRC).

    Phase II

    Measured: Up to 24 months

  4. To evaluate the safety of pirtobrutinib in combination with venetoclax (Arm A) by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0

    For Phase 1b

    Measured: Up to 24 Months

  5. To evaluate the safety of pirtobrutinib in combination with venetoclax and rituximab (Arm B) by assessing incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0

    For Phase 1b

    Measured: Up to 24 Months

Secondary outcomes (14)

  1. To determine the safety profile and tolerability of pirtobrutinib including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events.

    Phase I

    Measured: Up to 24 Months

  2. To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.

    Phase I

    Measured: Up to 24 Months

  3. To assess the preliminary anti-tumor activity of pirtobrutinib based on overall response rate (ORR) as assessed by investigator.

    Phase I

    Measured: Up to 24 Months

  4. ORR as assessed by the Investigator.

    Phase II

    Measured: Up to 24 Months

  5. Best overall response (BOR) as assessed by the Investigator and IRC.

    Phase II

    Measured: Up to 24 Months

  6. Duration of response (DOR) as assessed by the Investigator and IRC.

    Phase II

    Measured: Up to 24 Months

  7. Progression free survival (PFS) as assessed by the Investigator and IRC.

    Phase II

    Measured: Up to 24 Months

  8. Overall survival (OS).

    Phase II

    Measured: Up to 24 Months

  9. To determine the safety profile and tolerability of pirtobrutinib including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events

    Phase II

    Measured: Up to 24 Months

  10. To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.

    Phase II

    Measured: Up to 24 Months

  11. To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.

    For Phase 1b

    Measured: Up to 24 months

  12. To assess the preliminary anti-tumor activity of pirtobrutinib in combination based on overall response rate (ORR) as assessed by investigator.

    For Phase 1b

    Measured: Up to 24 months

  13. Symptomatic Response: Change from Baseline in Mantle Cell Lymphoma (MCL)-related symptoms selected from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library

    Individual EORTC symptom scores range from 1 (not at all) to 4 (very much) with higher scores representing more severe symptom severity.

    Measured: Baseline, End of Treatment (Estimated Up to 24 Months)

  14. Functional Response: Change from Baseline in Physical Functioning as Measured by Physical Functioning Scale from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ)

    EORTC physical function item scores range from 1 (not at all) to 4 (very much) with higher scores indicating poorer functioning.The total EORTC physical functioning score ranges from 0-100 where a higher score indicates higher/healthier level of functioning.

    Measured: Baseline, End of Treatment (Estimated Up to 24 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2018
  2. Study start15 Mar 2019
  3. Primary completion27 Jan 2025
  4. Study completion23 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
803 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03740529
Sponsor's protocol ID
17539
Other IDs
2018-003340-24, J2N-OX-JZNA, LOXO-BTK-18001 (BRUIN), 2018
Status last verified
Jan 2026
First submitted
6 Nov 2018
Last updated
27 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Expanded access
Available

Publications

  • Wang ML, Cohen JB, Shah NN, Jurczak W, Zinzani PL, Cheah CY, Ujjani CS, Koh Y, Kim WS, Nasta SD, Flinn I, Tessoulin B, Ma S, Alencar AJ, Lewis DJ, Woyach JA, Maddocks KJ, Patel K, Wang Y, Rhodes JM, Tam CS, Seymour JF, Nagai H, Vose JM, Fakhri B, Hoffmann MS, Hernandez-Ilizaliturri F, Zelenetz AD, Kumar A, Munir T, Tsai DE, Abada P, Balbas M, Li J, Wang D, Roeker LE, Eyre TA. Final Analysis of the BRUIN Phase 1/2 Study Assessing the Safety and Efficacy of Pirtobrutinib Monotherapy in Patients With MCL. Am J Hematol. 2026 Nov 4. doi: 10.1002/ajh.70533. Online ahead of print.

    PubMed 42983593

  • Bell R, O'Brien LM, Yuen E, Liu D, Chapman SC. Population pharmacokinetic analysis of pirtobrutinib, a non-covalent BTK inhibitor, in patients with hematological malignancies from the Phase 1/2 BRUIN study. Cancer Chemother Pharmacol. 2026 Sep 24;96(1):111. doi: 10.1007/s00280-026-04951-4.

    PubMed 42786239

  • Palomba ML, Patel MR, Eyre TA, Jurczak W, Lewis D, Gastinne T, Ma S, Cohen JB, Patel K, Brown JR, Scarfo L, Munir T, Lech-Maranda E, Hoffmann MS, Ujjani CS, Fakhri B, Wang ML, Izutsu K, Nagai H, Tam CS, Rhodes JM, Vose J, McKinney M, Gerson JN, Barve MA, Kuss B, Koh Y, Barrett A, Treon SP, Castillo JJ, Seymour JF, Ruppert AS, McNeely SC, Walgren RA, Tsai DE, Bao K, Nair B, Woyach J, Cheah CY. Safety and activity of pirtobrutinib in patients with relapsed or refractory Waldenstrom macroglobulinaemia: 5-year follow-up of the open-label, multicentre, phase 1/2 BRUIN trial. Lancet Haematol. 2026 May;13(5):e284-e296. doi: 10.1016/S2352-3026(26)00037-2.

    PubMed 42069409

  • Patel K, Vose JM, Nasta SD, Brown JR, Maddocks KJ, Woyach JA, Shah NN, Fakhri B, Tessoulin B, Ma S, Jagadeesh D, Lech-Maranda E, Coombs CC, Patel MR, Rhodes JM, Ujjani C, Hoffmann MS, Cheah CY, Munir T, Lewis D, Scarfo L, Eyre TA, Alencar A, Cohen JB, Zelenetz AD, Tsai DE, Li M, Bian Y, Abada P, Balbas M, Zinzani PL. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R marginal zone lymphoma: phase 1/2 BRUIN study. Blood Adv. 2026 Apr 14;10(7):2441-2451. doi: 10.1182/bloodadvances.2025017489.

    PubMed 41544219

  • Brown JR, Nguyen B, Desikan SP, Won H, Tantawy SI, McNeely SC, Marella N, Randeria HS, Hanson LM, Parker A, Botelho SC, Woyach JA, Patel K, Tam CS, Eyre TA, Cheah CY, Shah NN, Ghia P, Jurczak W, Balbas M, Nair B, Abada P, Wang C, Wang D, Roeker LE, Gandhi V, Wierda WG. Genomic determinants of response and resistance to pirtobrutinib in relapsed/refractory chronic lymphocytic leukemia. Blood. 2026 Jan 1;147(1):24-34. doi: 10.1182/blood.2024027009.

    PubMed 41055698

  • Shah NN, Zinzani PL, Wang M, Nasta SD, Lech-Maranda E, Ogawa Y, Fakhri B, Kuss B, Miyashita K, Patel K, Coombs CC, Ma S, Patel MR, Barve MA, Tessoulin B, Stathis A, Ennishi D, Hashimoto D, Kojima K, Zelenetz AD, Cohen JB, Vose JM, Maddocks KJ, Munir T, Sun F, Bian Y, Balbas M, Tsai DE, Abada P, Cheah CY. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi in R/R follicular lymphoma: phase 1/2 BRUIN study. Blood Adv. 2025 Dec 9;9(23):5954-5964. doi: 10.1182/bloodadvances.2024014975.

    PubMed 40845254

  • Lamanna N, Tam CS, Woyach JA, Alencar AJ, Palomba ML, Zinzani PL, Flinn IW, Fakhri B, Cohen JB, Kontos A, Konig H, Ruppert AS, Chatterjee A, Sizelove R, Compte L, Tsai DE, Jurczak W. Evaluation of bleeding risk in patients who received pirtobrutinib in the presence or absence of antithrombotic therapy. EJHaem. 2024 Sep 27;5(5):929-939. doi: 10.1002/jha2.1013. eCollection 2024 Oct.

    PubMed 39415923

  • Wierda WG, Shah NN, Cheah CY, Lewis D, Hoffmann MS, Coombs CC, Lamanna N, Ma S, Jagadeesh D, Munir T, Wang Y, Eyre TA, Rhodes JM, McKinney M, Lech-Maranda E, Tam CS, Jurczak W, Izutsu K, Alencar AJ, Patel MR, Seymour JF, Woyach JA, Thompson PA, Abada PB, Ho C, McNeely SC, Marella N, Nguyen B, Wang C, Ruppert AS, Nair B, Liu H, Tsai DE, Roeker LE, Ghia P. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study. Lancet Haematol. 2024 Sep;11(9):e682-e692. doi: 10.1016/S2352-3026(24)00172-8. Epub 2024 Jul 18.

    PubMed 39033770

  • Roeker LE, Woyach JA, Cheah CY, Coombs CC, Shah NN, Wierda WG, Patel MR, Lamanna N, Tsai DE, Nair B, Wang C, Zhao X, Liu D, Radtke D, Chapman S, Marella N, McNeely SC, Brown JR. Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: the phase 1b BRUIN trial. Blood. 2024 Sep 26;144(13):1374-1386. doi: 10.1182/blood.2024024510.

    PubMed 38861666

  • Telaraja D, Kasamon YL, Collazo JS, Leong R, Wang K, Li P, Dahmane E, Yang Y, Earp J, Grimstein M, Rodriguez LR, Theoret MR, Gormley NJ. FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma. Clin Cancer Res. 2024 Jan 5;30(1):17-22. doi: 10.1158/1078-0432.CCR-23-1272.

    PubMed 37624619

  • Mato AR, Woyach JA, Brown JR, Ghia P, Patel K, Eyre TA, Munir T, Lech-Maranda E, Lamanna N, Tam CS, Shah NN, Coombs CC, Ujjani CS, Fakhri B, Cheah CY, Patel MR, Alencar AJ, Cohen JB, Gerson JN, Flinn IW, Ma S, Jagadeesh D, Rhodes JM, Hernandez-Ilizaliturri F, Zinzani PL, Seymour JF, Balbas M, Nair B, Abada P, Wang C, Ruppert AS, Wang D, Tsai DE, Wierda WG, Jurczak W. Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jul 6;389(1):33-44. doi: 10.1056/NEJMoa2300696.

    PubMed 37407001

  • Wang ML, Jurczak W, Zinzani PL, Eyre TA, Cheah CY, Ujjani CS, Koh Y, Izutsu K, Gerson JN, Flinn I, Tessoulin B, Alencar AJ, Ma S, Lewis D, Lech-Maranda E, Rhodes J, Patel K, Maddocks K, Lamanna N, Wang Y, Tam CS, Munir T, Nagai H, Hernandez-Ilizaliturri F, Kumar A, Fenske TS, Seymour JF, Zelenetz AD, Nair B, Tsai DE, Balbas M, Walgren RA, Abada P, Wang C, Zhao J, Mato AR, Shah NN. Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma. J Clin Oncol. 2023 Aug 20;41(24):3988-3997. doi: 10.1200/JCO.23.00562. Epub 2023 May 16.

    PubMed 37192437

  • Aslan B, Kismali G, Iles LR, Manyam GC, Ayres ML, Chen LS, Gagea M, Bertilaccio MTS, Wierda WG, Gandhi V. Pirtobrutinib inhibits wild-type and mutant Bruton's tyrosine kinase-mediated signaling in chronic lymphocytic leukemia. Blood Cancer J. 2022 May 20;12(5):80. doi: 10.1038/s41408-022-00675-9.

    PubMed 35595730

  • Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.

    PubMed 34398557

  • Mato AR, Shah NN, Jurczak W, Cheah CY, Pagel JM, Woyach JA, Fakhri B, Eyre TA, Lamanna N, Patel MR, Alencar A, Lech-Maranda E, Wierda WG, Coombs CC, Gerson JN, Ghia P, Le Gouill S, Lewis DJ, Sundaram S, Cohen JB, Flinn IW, Tam CS, Barve MA, Kuss B, Taylor J, Abdel-Wahab O, Schuster SJ, Palomba ML, Lewis KL, Roeker LE, Davids MS, Tan XN, Fenske TS, Wallin J, Tsai DE, Ku NC, Zhu E, Chen J, Yin M, Nair B, Ebata K, Marella N, Brown JR, Wang M. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021 Mar 6;397(10277):892-901. doi: 10.1016/S0140-6736(21)00224-5.

    PubMed 33676628

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pirtobrutinib, Venetoclax and Rituximab in people with Chronic Lymphocytic Leukemia and Waldenstrom Macroglobulinemia, run by Loxo Oncology, Inc. at 56 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States, Japan, Australia, United Kingdom, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: Up to 24 Months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03740529, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.

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