Tremelimumab with or without durvalumab in combination with paclitaxel in metastatic urothelial cancer: phase I/II ICRA trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: New therapeutic strategies for patients with therapy-refractory metastatic urothelial carcinoma (mUC) are still needed. In the phase I-II ICRA trial, a multicenter, open-label, phase Ib-II clinical trial (NCT03871036), we evaluated whether paclitaxel plus tremelimumab, with or without durvalumab, could induce a tumor response in mUC following platinum chemotherapy and immune checkpoint inhibition (ICI). Patients were randomized between three arms: A (n = 20) paclitaxel plus T750mg; B (n = 12) paclitaxel plus T300mg plus D1500mg; C (n = 12) T750mg. The primary outcome, objective response rate, was met with 26% in arm A (88% CI = [14,36%]) versus 17% (88% CI = [3,42%]) in arm B and 8% (88% CI = [0.3,33%]) in arm C. Secondary outcomes included safety, duration of response and survival. Grade 3-4 treatment-related adverse events occurred in (A) 45%, (B) 75%, and (C) 25% of patients. Murine experiments showed attenuated tumor outgrowth for paclitaxel plus anti-CTLA-4 compared to monotherapy with either agent. Transcriptomic analyses showed upregulation of inflammation signatures in on-treatment tumor tissue biopsies. This study demonstrated encouraging antitumor activity in therapy-refractory mUC treated with paclitaxel plus high-dose anti-CTLA-4 and suggests immune induction may still be possible after failure to anti-PD-(L)1 therapy. Therapeutic options for patients with treatment-refractory metastatic urothelial carcinoma (mUC) are much needed. Here, the authors report the outcomes and translational analysis of the phase I/II ICRA trial evaluating whether paclitaxel plus tremelimumab (anti-CTLA-4) with or without durvalumab (anti-PD-L1) induces a tumor response in patients with mUC.
Source: Nature Communications
Authors: Sarah M. H. Einerhand, Hamza Ali, Stephen Q. Wong, Jeroen van Dorp, Tatum van Maanen, Jeantine M. de Feijter, Maurits L. van Montfoort, Thierry N. Boellaard, Linde M. Braaf, Wim Brugman, Daniel J. Vis, Cindy M. J. Hollander, Antonios Daletzakis, Helga A. Schrijver, Karen Snapper, Sjoukje F. Oosting, Cheryl P. Bruijnen, Lodewyk F. A. Wessels, Keith S. Chan, Britt B. M. Suelmann, Michiel S. van der Heijden
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7165006353
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