Mp63-13 trials in progress: a phase i/ii trial of intravesical chemoimmunotherapy with gemcitabine and bacillus calmette-guérin (bcg) for patients with bcg-exposed high-grade non-muscle invasive bladder cancer (nmibc)

You have accessJournal of UrologyCME1 Apr 2023MP63-13 TRIALS IN PROGRESS: A PHASE I/II TRIAL OF INTRAVESICAL CHEMOIMMUNOTHERAPY WITH GEMCITABINE AND BACILLUS CALMETTE-GUÉRIN (BCG) FOR PATIENTS WITH BCG-EXPOSED HIGH-GRADE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) Christopher Gaffney, NEETA D'Souza, Christian Hernandez, Melissa McCarter, Patricia Moran, Kristen Staci, Kara Worth, Guido Dalbagni, Timothy Donahue, Sherri Donat, Bernard Bochner, Judy Sarungbam, Dean Bajorin, Hikmat AL-Ahmadie, Daniel Sjoberg, Alvin Goh, and Eugene Pietzak Christopher GaffneyChristopher Gaffney More articles by this author , NEETA D'SouzaNEETA D'Souza More articles by this author , Christian HernandezChristian Hernandez More articles by this author , Melissa McCarterMelissa McCarter More articles by this author , Patricia MoranPatricia Moran More articles by this author , Kristen StaciKristen Staci More articles by this author , Kara WorthKara Worth More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Timothy DonahueTimothy Donahue More articles by this author , Sherri DonatSherri Donat More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Judy SarungbamJudy Sarungbam More articles by this author , Dean BajorinDean Bajorin More articles by this author , Hikmat AL-AhmadieHikmat AL-Ahmadie More articles by this author , Daniel SjobergDaniel Sjoberg More articles by this author , Alvin GohAlvin Goh More articles by this author , and Eugene PietzakEugene Pietzak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The standard of care for high-risk NMIBC after exposure to induction only BCG or relapse >12 months after “adequate” BCG is retreatment with BCG. However, ∼50% will relapse within 6 months. Intravesical Gemcitabine (GEM) is a well-tolerated, common treatment for NMIBC with better efficacy after BCG than mitomycin C which may synergistically enhance the efficacy of BCG by augmenting the immune tumor microenvironment. We are evaluating gemcitabine and BCG (GemBCG) intravesical chemoimmunotherapy to address the need for more effective and less toxic bladder preserving treatments by enhancing BCG efficacy. METHODS: This is an investigator-initiated Phase I/II trial of GemBCG for BCG-exposed NMIBC enrolling patients with BCG-exposed carcinoma in-situ (CIS±Ta/T1) that recurred within 24 months of last BCG (BCG-exposed/BCG-relapsing NMIBC, Figure 1). Patients with BCG-unresponsive disease, contraindication to BCG, or prostatic/ureteral urothelial disease are excluded. The primary endpoint for Phase I was safety and dose tolerability. The primary endpoint for Phase II is clinical complete response (CR) at 6 months (absence of high-grade disease on cystoscopy/TURBT and negative cytology). Using a Simon’s optimal 2-stage design testing the null hypothesis of a true CR of 55% at 6 months (based on historical outcomes of BCG alone) we plan to enroll 19 and 24 patients in the first and second stage, respectively. Phase I patients treated at the maximum tolerated dose (MTD) are included in phase II. Secondary outcomes include recurrence progression, and cystectomy-free survival. Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. RESULTS: Of the 25 patients who completed Phase I, 14/25 were treated at the MTD and processed to Phase II. Treatment was well-tolerated (no treatment related grade ≥3 adverse events) and demonstrated promising early efficacy (95% [19/20] CR at 6-months). CONCLUSIONS: A combination of intravesical GEM and BCG appears safe and well tolerated in patients with BCG-relapsed/BCG-exposed NMIBC. Promising early efficacy data requires completion of Phase II for confirmation (NCT04179162). Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e876 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Gaffney More articles by this author NEETA D'Souza More articles by this author Christian Hernandez More articles by this author Melissa McCarter More articles by this author Patricia Moran More articles by this author Kristen Staci More articles by this author Kara Worth More articles by this author Guido Dalbagni More articles by this author Timothy Donahue More articles by this author Sherri Donat More articles by this author Bernard Bochner More articles by this author Judy Sarungbam More articles by this author Dean Bajorin More articles by this author Hikmat AL-Ahmadie More articles by this author Daniel Sjoberg More articles by this author Alvin Goh More articles by this author Eugene Pietzak More articles by this author Expand All Advertisement PDF downloadLoading ...