The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial.

Neoadjuvant chemotherapy and radical cystectomy (RC) are underutilized standards of care for the treatment of muscle-invasive bladder cancer (MIBC) due to high patient burden from systemic toxicities and postoperative complications, respectively. TAR-200 is a novel intravesical drug delivery system developed to release gemcitabine into the bladder urine continuously, resulting in distribution of drug into stromal layers of the bladder. The primary aim of the TAR-200-101 study was to evaluate the safety of TAR-200 in patients with MIBC prior to RC (NCT02722538).

This phase I, open-label study was conducted across 6 US and European sites. Eligible patients were aged ≥18 years with histologically confirmed T2a-T3b N0-N1 M0 urothelial cancer and had refusal or were ineligible to receive cisplatin-based combination chemotherapy. Two arms were enrolled serially. Patients in Arm 1 had residual tumor >3 cm after transurethral resection of bladder tumor (TURBT); those in Arm 2 had undergone maximal TURBT (residual tumor <3 cm). Patients received two 7-day cycles of intravesical gemcitabine delivery via TAR-200 before undergoing RC. Primary outcome was safety; secondary outcomes were tolerability, pharmacokinetics, and preliminary efficacy.

Of 23 patients in the intention-to-treat population (11 in Arm 1, 12 in Arm 2), 20 completed both dosing cycles of TAR-200. No patients were classified as intolerant to TAR-200. Ten patients (4 in Arm 1, 6 in Arm 2) experienced ≥1 treatment-emergent adverse events (TEAEs). The most common TAR-200-related TEAEs were pollakiuria (n = 3) and urinary incontinence (n = 2). All TEAEs prior to RC were grade ≤2; 1 patient in Arm 2 experienced a grade 3 non-treatment-related TEAE. Plasma gemcitabine levels were undetectable. In Arm 1, those with residual tumor, 4 of 10 patients exhibited pathologic downstaging; 1 experienced a complete response (CR) and 3 a partial response (PR). In Arm 2, those undergoing maximal TURBT, 6 of 10 patients exhibited downstaging; 3 experienced a CR and 3 a PR.

Controlled intravesical gemcitabine release via TAR-200 was safe and well tolerated in patients with MIBC.

Urologic oncology. 2022 Apr 14 [Epub]

Siamak Daneshmand, Iris S G Brummelhuis, Kamal S Pohar, Gary D Steinberg, Manju Aron, Christopher J Cutie, Kirk A Keegan, John C Maffeo, Donald L Reynolds, Bradley Raybold, Albert Chau, J Alfred Witjes

Department of Urology, University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA. Electronic address: ., Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands., Department of Urology, College of Medicine, The Ohio State University, Columbus, OH., Department of Urology, NYU Langone Health, New York, NY., Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA., Janssen Research & Development, Lexington, MA., Janssen Research & Development, Spring House, PA., Datacision Limited, London, UK.