Journal article
A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer
Urologic oncology, v 35(2), pp 39.e1-39.e7
Feb 2017
PMID: 28341495
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Imiquimod is a toll-like receptor agonist with proven antitumor activity as a topical treatment for skin cancer. TMX-101 (Vesimune) is a novel liquid formulation of imiquimod optimized for intravesical delivery. The agent demonstrated safety as an intravesical treatment for non–muscle-invasive bladder cancer in a phase 1 clinical trial. We report the results of a phase 2 prospective multicenter clinical trial assessing the safety and activity of TMX-101.
Patients with non–muscle-invasive bladder cancer containing carcinoma in situ were eligible for inclusion. Enrolled patients received 6 weekly intravesical administrations of 200mg/50ml TMX-101 0.4%. End points included rate of adverse events, changes in urinary cytokine levels following treatment, and clinical response at 6 weeks following final instillation, defined as negative posttreatment bladder biopsy and urine cytology results.
A total of 12 patients were enrolled, with 10 available for efficacy analysis. Half of the patients (6/12) had received≥2 prior induction courses of bacillus Calmette-Guerin. All patients received all 6 doses of TMX-101 per protocol. Overall, 75% of patients experienced treatment-related adverse events, only 1 of which was>grade 2 (urinary tract infection). Furthermore, 2 patients demonstrated a negative cytology and biopsy result at 6 weeks following treatment. Significant increases in urinary cytokines, including IL-6 and IL-18, were seen following treatment.
In this phase 2 pilot study in patients with carcinoma in situ bladder cancer, intravesical TMX-101 was safe and well tolerated with common, mild genitourinary adverse effects. Clinical activity was suggested by the increase in posttreatment urinary cytokines. Complete responders were seen. Further investigation of the agent is warranted.
•TMX-101 0.4% is a novel intravesical formulation of imiquimod, a toll-like receptor agonist.•In this phase-2 study of patients with CIS, TMX-101 had an excellent safety profile.•Activity was suggested by significant increases in urinary cytokines including IL-18.•A total of 2 patients demonstrated a complete response 6 weeks following treatment.
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Details
- Title
- A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer
- Creators
- Nicholas M. Donin - University of California, Los AngelesKarim Chamie - University of California, Los AngelesAndrew T. Lenis - University of California, Los AngelesAllan J. Pantuck - Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CAMadhu Reddy - Hahnemann University HospitalDana Kivlin - Hahnemann University HospitalJohanna Holldack - Telormedix SA, Bioggio, Switzerland.Rafaella Pozzi - Telormedix SA, Bioggio, Switzerland.Gil Hakim - UroGen Pharma, Ra'anana, Israel.Lawrence I. Karsh - The Urology Center of ColoradoDonald L. Lamm - Arizona OncologyLaurence H. Belkoff - Hahnemann University HospitalArie S. Belldegrun - University of California, Los AngelesStuart Holden - University of California, Los AngelesNeal Shore - Carolina Urologic Research Center
- Publication Details
- Urologic oncology, v 35(2), pp 39.e1-39.e7
- Publisher
- Elsevier
- Grant note
- Seventh Framework Programme
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000392645300007
- Scopus ID
- 2-s2.0-84994059878
- Other Identifier
- 991019168847004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology
- Urology & Nephrology