Results from a phase 1b/2 study of ibrutinib combination therapy in advanced urothelial carcinoma

Mar, N. et al. (2023) Results from a phase 1b/2 study of ibrutinib combination therapy in advanced urothelial carcinoma. Cancers, 15(11), 2978. (doi: 10.3390/cancers15112978) (PMID:37296940) (PMCID:PMC10251876)

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.

• Item Type: Articles
• Additional Information: This study was sponsored by Pharmacyclics LLC, an AbbVie Company.
• Keywords: Paclitaxel, pembrolizumab, urothelial carcinoma, ibrutinib.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jones, Professor Robert
• Authors: Mar, N., Zakharia, Y., Falcon, A., Morales-Barrera, R., Mellado, B., Duran, I., Oh, D.-Y., Williamson, S. K., Gajate, P., Arkenau, H.-T., Jones, R. J., Teo, M. Y., Turan, T., McLaughlin, R. T., Peltier, H. M., Chong, E., Atluri, H., Dean, J. P., and Castellano, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancers
• Publisher: MDPI
• ISSN: 2072-6694
• ISSN (Online): 2072-6694
• Published Online: 30 May 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Cancers 15(11): 2978
• Publisher Policy: Reproduced under a Creative Commons License