Phase 1/2 Trial Results of a Large Surface Area Microparticle Docetaxel for the Treatment of High-Risk Non-muscle Invasive Bladder Cancer.

We investigated the safety, preliminary efficacy, and immune effects of large surface area microparticle docetaxel (LSAM-DTX) administered by direct-injection after transurethral resection of bladder tumor (TURBT) and by intravesical instillation in high-risk non-muscle invasive bladder cancer (NMIBC).

The trial followed an open-label 3+3 dose-escalation with additional enrollment at the high-dose. After TURBT, subjects received direct-injection LSAM-DTX into the resection site and intravesical LSAM-DTX, followed by 6-week induction and 3-week maintenance intravesical LSAM-DTX courses. Tumor recurrence was evaluated by cytology, cystoscopy, or biopsy. Pharmacokinetic analysis of blood and multiplex immunofluorescence of tumor microenvironment occurred pre- and post-LSAM-DTX.

Nineteen subjects were enrolled, 14 with prior bacillus Calmette-Guérin (BCG) exposure and 16 with ≥1 prior TURBT. Direct-injection and intravesical LSAM-DTX were well-tolerated. In the three lowest dose-escalation cohorts the median recurrence free survival (RFS) was 5.4-months (n=10; median follow-up = 8.6-months). In the high dose and expansion cohorts median RFS was significantly increased (p<0.05; hazard ratio=0.29) to 12.2-months (n=9; median follow-up = 12.4-months). Systemic docetaxel exposure was negligible and increases in anti-tumor immune cells were found in the tumor microenvironment along with elevations in the PD-1, PD-L1 and CTLA-4 immune checkpoint inhibitor) targets.

Post-TURBT direct-injection and intravesical LSAM-DTX was well tolerated and demonstrated clinical response for patients with high-risk NMIBC. Favorable immune cell infiltration and checkpoint receptor increases following LSAM-DTX treatment warrants investigation alone as well as in combination with immune checkpoint inhibitor therapy.

The Journal of urology. 2022 May 16 [Epub ahead of print]

Max Kates, Ahmed M Mansour, Donald L Lamm, Neal Shore, Holly Maulhardt, Alison Wendt, James Verco, Alyson Marin, Karan Dewnani, Shelagh Verco, Gere S diZerega

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland., UT Health San Antonio, San Antonio, Texas., BCG Oncology, PC, Phoenix, Arizona., Carolina Urologic Research Center, Myrtle Beach, South Carolina., US Biotest, Inc., San Luis Obispo, California., DFB Pharmaceuticals, Inc., Fort Worth, Texas.

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