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Cited by 466

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study

Open access
Mato, Anthony R, Shah, Nirav N, Jurczak, Wojciech, Cheah, Chan Y, Pagel, John M, Woyach, Jennifer A, Fakhri, Bita, Eyre, Toby A, Lamanna, Nicole, Patel, Manish R, Alencar, Alvaro, Lech-Maranda, Ewa, Wierda, William G, Coombs, Catherine C, Gerson, James N, Ghia, Paolo, Le Gouill, Steven, Lewis, David John, Sundaram, Suchitra, Cohen, Jonathon B, Flinn, Ian W, Tam, Constantine S, Barve, Minal A, Kuss, Bryone, Taylor, Justin, Abdel-Wahab, Omar, Schuster, Stephen J, Palomba, M Lia, Lewis, Katharine L, Roeker, Lindsey E, Davids, Matthew S, Tan, Xuan Ni, Fenske, Timothy S, Wallin, Johan, Tsai, Donald E, Ku, Nora C, Zhu, Edward, Chen, Jessica, Yin, Ming, Nair, Binoj, Ebata, Kevin, Marella, Narasimha, Brown, Jennifer R, Wang, Michael·2021·The Lancet
DOI 10.1016/s0140-6736(21)00224-5
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Abstract

SUMMARY Background: Covalent BTK inhibitors (cBTKi) are efficacious in multiple B-cell malignancies but patients discontinue these agents due to resistance and intolerance. We evaluated the safety and efficacy of LOXO-305, a highly selective, reversible BTK inhibitor in these patients. Methods: Patients with previously treated B-cell malignancies were enrolled in a first-in-human, multi-centre, open-label, phase 1/2 trial. The primary endpoint was the maximum tolerated dose (MTD) (phase 1) and ORR (phase 2). Findings: 323 patients were treated with LOXO-305 across seven dose levels (25 mg to 300 mg once daily) with linear dose-proportional exposures. No DLTs were observed and the MTD was not reached. Recommended phase 2 dose was 200 mg daily. Adverse events in ≥10% of patients were fatigue (20%), diarrhoea (17%), and contusion (13%). The most common grade ≥3 adverse event was neutropenia (10%). There was no correlation between LOXO-305 exposure and the frequency of grade 3 treatment-related adverse events. Grade 3 atrial fibrillation/flutter was not observed, and grade 3 hemorrhage was observed in 1 patient in the setting of mechanical trauma. Five patients (1.5%) discontinued treatment due to a treatment-related adverse event. In 121 efficacy evaluable cBTKi-treated CLL patients (median prior lines = 4), ORR was 62% (95% CI: 53–71). ORR was similar in CLL/SLL patients with prior cBTKi resistance (67%, 53/79), cBTKi intolerance (52%, 22/42), BTK C481-mutant (71%, 17/24) and BTK-wildtype (66%, 43/65) disease. In 52 efficacy evaluable cBTKi-treated MCL patients, the ORR was 52% (95% CI: 38–66). Of 117 responding CLL or MCL patients, all but eight remain progression-free. Interpretation: LOXO-305 was safe and active in multiple B-cell malignancies, including patients previously treated with cBTKi. LOXO-305 may address a growing unmet need for alternative therapies for these patients. Funding: Loxo Oncology, a subsidiary of Eli Lilly. Trial Registry: Clinicaltrials.gov NCT03740529

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Metadata

Authors
Mato, A. R., Shah, N. N., Jurczak, W., Cheah, C. Y., Pagel, J. M., Woyach, J. A., Fakhri, B., Eyre, T. A., Lamanna, N., Patel, M. R., Alencar, A., Lech-Maranda, E., Wierda, W. G., Coombs, C. C., Gerson, J. N., Ghia, P., Le Gouill, S., Lewis, D. J., Sundaram, S., Cohen, J. B., Flinn, I. W., Tam, C. S., Barve, M. A., Kuss, B., Taylor, J., Abdel-Wahab, O., Schuster, S. J., Palomba, M. L., Lewis, K. L., Roeker, L. E., Davids, M. S., Tan, X. N., Fenske, T. S., Wallin, J., Tsai, D. E., Ku, N. C., Zhu, E., Chen, J., Yin, M., Nair, B., Ebata, K., Marella, N., Brown, J. R., & Wang, M.
Venue
The Lancet
Publisher
Elsevier BV
Published
2021-03
Volume
397
Issue
10277
Pages
892-901
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(21)00224-5
OpenAlex
W3134524629
Cited by
466
References
27
FWCI
39.22
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. https://app.cochat.ai/papers/10.1016/s0140-6736(21)00224-5
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Mato, A. R., Shah, N. N., Jurczak, W., Cheah, C. Y., Pagel, J. M., Woyach, J. A., Fakhri, B., Eyre, T. A., Lamanna, N., Patel, M. R., Alencar, A., Lech-Maranda, E., Wierda, W. G., Coombs, C. C., Gerson, J. N., Ghia, P., Le Gouill, S., Lewis, D. J., Sundaram, S., . . . Wang, M. (2021). Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. The Lancet. https://doi.org/10.1016/s0140-6736(21)00224-5

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.