A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer.
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.
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA. Electronic address: NDonin@mednet.ucla.edu.
Nicholas M
NM
Donin
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.
Karim
K
Chamie
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.
Andrew T
AT
Lenis
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.
Allan J
AJ
Pantuck
Division of Urology, Hahnemann University Hospital, Philadephia, PA.
Madhu
M
Reddy
Division of Urology, Hahnemann University Hospital, Philadephia, PA.
Dana
D
Kivlin
Telormedix SA, Bioggio, Switzerland.
Johanna
J
Holldack
Telormedix SA, Bioggio, Switzerland.
Rafaella
R
Pozzi
UroGen Pharma, Ra'anana, Israel.
Gil
G
Hakim
The Urology Center of Colorado, Denver, CO.
Lawrence I
LI
Karsh
BCG Oncology, Phoenix, AZ.
Donald L
DL
Lamm
Division of Urology, Hahnemann University Hospital, Philadephia, PA.
Laurence H
LH
Belkoff
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.
Arie S
AS
Belldegrun
Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA.
Stuart
S
Holden
Carolina Urologic Research Center, Myrtle Beach, SC.
Neal
N
Shore
D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000652:urine; D016207:Cytokines / Q000652:urine; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D000077271:Imiquimod; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000652:urine
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D016207:Cytokines; D000077271:Imiquimod
Administrations, intravesical drug; Carcinoma in situ; Imiquimod; Immunotherapy; Urinary bladder neoplasms