A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer

Journal of Urologic Oncology, 2016

Nicholas M. Donin, Karim Chamie, Andrew T. Lenis, Allan J. Pantuck, Madhu Reddy, Dana Kivlin, Johanna Holldack, Rafaella Pozzi, and others


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.


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.Materials and methods

Patients with non–muscle-invasive bladder cancer containing carcinoma in situ were eligible for inclusion. Enrolled patients received 6 weekly intravesical administrations of 200 mg/50 ml 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.

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