A Phase I Clinical Trial of Chemoimmunotherapy with Alternating Intravesical Gemcitabine and Bacillus Calmette-Guérin (GemBCG) for BCG-Exposed High-Grade Non-Muscle-Invasive Bladder Cancer.

Authors

Christopher D Gaffney, Syed Muneeb Alam, Gal Wald, Daniel Sjoberg, Jordan Eichholz, Judy Sarungbam, Neeta D'Souza, Jessica Lavery, Christian Hernandez, Morgan Tomerlein, Patricia Zagajeski, Kara Worth Hildreth, Sherri Donat, Robert Smith, Timothy Donahue, Alvin Goh, Bernard Bochner, Hikmat Al-Ahmadie, Eugene Pietzak

Published in

The Journal of urology. Pages 101097JU0000000000005324. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Retreatment with BCG alone is recommended for patients with Bacillus Calmette-Guérin (BCG)-exposed non-muscle-invasive bladder cancer (NMIBC), yet ∼50% recur and become "BCG-unresponsive." Strategies to improve the efficacy of BCG retreatment are urgently needed.
In this Phase I dose-escalation trial of intravesical chemoimmunotherapy with gemcitabine and BCG (GemBCG) in patients with BCG-exposed high-grade NMIBC (NCT04179162), Biweekly intravesical gemcitabine was given weeks 1, 4, 7, and 10 (8 doses total escalated from 500-2000 mg via a modified continual reassessment method) and weekly intravesical BCG (50 mg TICE) during weeks 2, 3, 5, 6, 8, and 9 (6 doses total). The primary objective was to define the maximally tolerated dose. Adverse events were assessed using CTCAE v5.0. The key secondary outcome was complete clinical response at 6-months. Analyses of tumor, urine, and blood samples were exploratory.
25 patients enrolled (median age 68 [IQR 64-75]) of whom 17 (68%) had CIS ± papillary disease. No treatment-related grade ≥3 AEs or dose-limiting toxicities occurred; 72% reported grade 1 and 20% reported grade 2 AEs. 24 of 25 patients (96%; 95%CI 80%-100%) achieved a complete clinical response at 6-months. T-cell recruitment chemokines (CXCL9, CXCL10, and CXCL11) increased and the immunosuppressive cytokine IL-6 decreased in the urine with treatment.
GemBCG was safe, well-tolerated, and demonstrated promising early efficacy and modification of the tumor microenvironment. Based on these data, a randomized phase III trial is testing GemBCG vs. retreatment with BCG alone for BCG exposed high-grade NMIBC (Alliance A032303/NCT07000084).

PMID:
42821609
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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