A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL
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)
4 other identifiers
interventional
803
10 countries
56
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2019
Longer than P75 for phase_1
56 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
November 6, 2018
CompletedFirst Posted
Study publicly available on registry
November 14, 2018
CompletedStudy Start
First participant enrolled
March 15, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 27, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 23, 2025
CompletedJanuary 27, 2026
January 1, 2026
5.9 years
November 6, 2018
January 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Maximum Tolerated Dose (MTD)
Phase I
Up to 24 Months
Recommended dose for further study
Phase I
Up to 24 Months
To assess the preliminary anti-tumor activity of pirtobrutinib based on ORR as assessed by an Independent Review Committee (IRC).
Phase II
Up to 24 months
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
Up to 24 Months
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
Up to 24 Months
Secondary Outcomes (14)
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.
Up to 24 Months
To characterize the pharmacokinetics (PK) properties of pirtobrutinib by collecting and evaluating serum at protocol specified time points.
Up to 24 Months
To assess the preliminary anti-tumor activity of pirtobrutinib based on overall response rate (ORR) as assessed by investigator.
Up to 24 Months
ORR as assessed by the Investigator.
Up to 24 Months
Best overall response (BOR) as assessed by the Investigator and IRC.
Up to 24 Months
- +9 more secondary outcomes
Study Arms (11)
Phase I Dose Escalation (Pirtobrutinib Monotherapy)
EXPERIMENTALDose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated
Phase 2 (Pirtobrutinib Monotherapy) Cohort 3
EXPERIMENTALCLL/SLL patients with no prior therapy.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 1
EXPERIMENTALNon-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 4
EXPERIMENTALCLL/SLL patients treated with prior therapy, BTK inhibitor naĂ¯ve.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 2
EXPERIMENTALCLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 5
EXPERIMENTALWM patients treated with a prior BTK inhibitor-containing regimen.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 6
EXPERIMENTALMZL patients treated with a prior BTK inhibitor-containing regimen.
Phase 2 (Pirtobrutinib Monotherapy) Cohort 7
EXPERIMENTALDefined 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.
Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm A
EXPERIMENTALRelapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax
Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm B
EXPERIMENTALRelapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab
Phase 1 Dose Expansion (Pirtobrutinib Monotherapy)
EXPERIMENTALPatients to receive the recommended Phase 2 dose of pirtobrutinib
Interventions
Oral
Oral
IV
Eligibility Criteria
You may qualify if:
- 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.
- 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.
You may not qualify if:
- 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.
- 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.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companycollaborator
- Loxo Oncology, Inc.lead
Study Sites (56)
Mayo Clinic of Scottsdale
Scottsdale, Arizona, 85259, United States
Scripps Coastal Medical Center
San Diego, California, 92103, United States
University of California San Francisco, Medical Center at Paranassus
San Francisco, California, 94117, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510, United States
Mayo Clinic-Jacksonville
Jacksonville, Florida, 32224, United States
Florida Cancer Specialists ORLANDO/DDU
Lake Mary, Florida, 32746, United States
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Florida Cancer Specialists
Sarasota, Florida, 34232, United States
Emory Clinic
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905-0002, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68105, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Northwell Health
New Hyde Park, New York, 11042, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Durham VA Medical Center
Durham, North Carolina, 27705, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Hospital
Columbus, Ohio, 43210, United States
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104, United States
Sarah Cannon Research Institute SCRI
Nashville, Tennessee, 37203, United States
Mary Crowley Cancer Research Center
Dallas, Texas, 75230, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Utah Cancer Specialists
Salt Lake City, Utah, 84106, United States
Swedish Medical Center
Seattle, Washington, 98104, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98195, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Linear Clinical Research
Nedlands, Western Australia, 6009, Australia
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hĂ´tel-Dieu
Nantes, 44093, France
IRCCS - AOU di Bologna
Bologna, 40138, Italy
IRCCS Ospedale San Raffaele
Milan, 20132, Italy
Nagoya Medical Center
Nagoya, Aichi-ken, 460-0001, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648, Japan
Tokai University Hospital- Isehara Campus
Isehara, Kanagawa, 259-1193, Japan
Kochi Medical School Hospital
Nankoku, Kochi, 783-8505, Japan
Tohoku University Hospital
Sendai, Miyagi, 980-8574, Japan
National Cancer Center Hospital
Chuo Ku, Tokyo, 104-0045, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1395, Japan
Kyoto Furitsu Medical University Hospital
Kyoto, 602-8566, Japan
Okayama University Hospital
Okayama, 700-8558, Japan
Kindai University Hospital
Osakasayama-Shi, 589-8511, Japan
Pratia MCM Krakow
Krakow, 30-510, Poland
Instytut Hermatologii I Transfuzjologii
Warsaw, Poland
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 06351, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Karolinska Institutet
Solna, AB, 171 65, Sweden
Ospedale Regionale Bellinzona e Valli
Bellinzona, Canton Ticino, 6500, Switzerland
St James's University Hospital
Leeds, LS9 7TF, United Kingdom
Churchill Hospital
Oxford, OX3 7LJ, United Kingdom
Derriford Hospital
Plymouth, Pl6 8DH, United Kingdom
Related Publications (12)
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 CS, Hoffmann MS, Cheah CY, Munir T, Lewis DJ, Scarfo L, Eyre TA, Alencar AJ, Cohen JB, Zelenetz AD, Tsai DE, Li M, Bian Y, Abada PB, Balbas M, Zinzani PLL. Pirtobrutinib, a Highly Selective, Non-covalent (Reversible) BTKi in R/R Marginal Zone Lymphoma: Phase 1/2 BRUIN Study. Blood Adv. 2026 Jan 16:bloodadvances.2025017489. doi: 10.1182/bloodadvances.2025017489. Online ahead of print.
PMID: 41544219DERIVEDBrown 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.
PMID: 41055698DERIVEDShah 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.
PMID: 40845254DERIVEDLamanna 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.
PMID: 39415923DERIVEDWierda 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.
PMID: 39033770DERIVEDRoeker 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.
PMID: 38861666DERIVEDTelaraja 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.
PMID: 37624619DERIVEDMato 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.
PMID: 37407001DERIVEDWang 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.
PMID: 37192437DERIVEDAslan 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.
PMID: 35595730DERIVEDKipps 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.
PMID: 34398557DERIVEDMato 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.
PMID: 33676628DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Donald Tsai, MD, PhD
Loxo Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
November 6, 2018
First Posted
November 14, 2018
Study Start
March 15, 2019
Primary Completion
January 27, 2025
Study Completion
December 23, 2025
Last Updated
January 27, 2026
Record last verified: 2026-01