Journal article
Results from a Phase 1b/2 Study of Ibrutinib Combination Therapy in Advanced Urothelial Carcinoma
Cancers, Vol.15(11), p.2978
05/30/2023
DOI: 10.3390/cancers15112978
PMCID: PMC10251876
PMID: 37296940
Abstract
Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab). Phase 1b determined the recommended phase 2 dose (RP2D) of ibrutinib, and phase 2 assessed progression-free survival (PFS), overall response rate (ORR), and safety. Thirty-five, eighteen, and fifty-nine patients received ibrutinib, ibrutinib plus pembrolizumab, and ibrutinib plus paclitaxel at the RP2D, respectively. Safety profiles were consistent with those of the individual agents. The best-confirmed ORRs were 7% (two partial responses) with single-agent ibrutinib and 36% (five partial responses) with ibrutinib plus pembrolizumab. Median PFS was 4.1 months (range, 1.0-37.4+) with ibrutinib plus paclitaxel. The best-confirmed ORR was 26% (two complete responses). In previously treated patients with UC, ORR was higher with ibrutinib plus pembrolizumab than with either agent alone (historical data in the intent-to-treat population). ORR with ibrutinib plus paclitaxel was greater than historical values for single-agent paclitaxel or ibrutinib. These data warrant further evaluation of ibrutinib combinations in UC.
Details
- Title: Subtitle
- Results from a Phase 1b/2 Study of Ibrutinib Combination Therapy in Advanced Urothelial Carcinoma
- Creators
- Nataliya Mar - University of California, IrvineYousef Zakharia - University of Iowa Hospitals and ClinicsAlejandro Falcon - Hospital Universitario Virgen del RocíoRafael Morales-Barrera - Universitat Autònoma de BarcelonaBegona Mellado - Universitat de BarcelonaIgnacio Duran - Instituto de Investigación Marqués de ValdecillaDo-Youn Oh - Seoul National University HospitalStephen K Williamson - The University of Kansas Health SystemPablo Gajate - Hospital Universitario Ramón y CajalHendrik-Tobias Arkenau - Sarah Cannon Research Institute United Kingdom (SCRI-UK) and University College London Cancer Institute, London W1G 6AD, UKRobert J Jones - Beatson West of Scotland Cancer CentreMin Yuen Teo - Memorial Sloan Kettering Cancer CenterTolga Turan - Pharmacyclics (United States)Robert T McLaughlin - Pharmacyclics (United States)Hillary M Peltier - Pharmacyclics (United States)Elizabeth Chong - Pharmacyclics (United States)Harisha Atluri - Pharmacyclics (United States)James P Dean - AbbVie (United States)Daniel Castellano - Hospital Universitario 12 De Octubre
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.15(11), p.2978
- DOI
- 10.3390/cancers15112978
- PMID
- 37296940
- PMCID
- PMC10251876
- NLM abbreviation
- Cancers (Basel)
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Grant note
- NA / Pharmacyclics (United States)
- Language
- English
- Date published
- 05/30/2023
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984544950002771
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