NCT03740529

Podcasts, YouTube videos and X posts in our index that name this trial. A report screens them, searches for more and cites what clinicians said when it is built.

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)

Phase

Phase 1/Phase 2

Status

Completed

Conditions

Chronic Lymphocytic Leukemia; Waldenstrom Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; B-cell Lymphoma; Small Lymphocytic Lymphoma

Interventions

Pirtobrutinib; Venetoclax; Rituximab

Arms

• Phase I Dose Escalation (Pirtobrutinib Monotherapy) · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 3 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 1 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 4 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 2 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 5 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 6 · Experimental
• Phase 2 (Pirtobrutinib Monotherapy) Cohort 7 · Experimental
• Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm A · Experimental
• Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm B · Experimental
• Phase 1 Dose Expansion (Pirtobrutinib Monotherapy) · Experimental

Enrollment

803

Primary outcomes

• Maximum Tolerated Dose (MTD)
• Recommended dose for further study
• To assess the preliminary anti-tumor activity of pirtobrutinib based on ORR as assessed by an Independent Review Committee (IRC).
• 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
• 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

Sponsor

Loxo Oncology, Inc. with Eli Lilly and Company

Start

Mar 15, 2019

Primary completion

Jan 27, 2025

Results posted

No

Registry record

NCT03740529 · updated Jan 27, 2026

• 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