Mp16-17 Phase I Study of Intravesical Fc-Optimized Anti-Cd40 Agonist Antibody 2141-V11 for Non-Muscle Invasive Bladder Cancer (Nmibc) Unresponsive to Bacillus Calmette-Guerin (Bcg)

You have accessJournal of UrologyBladder Cancer: Non-invasive I (MP16)1 May 2024MP16-17 PHASE I STUDY OF INTRAVESICAL FC-OPTIMIZED ANTI-CD40 AGONIST ANTIBODY 2141-V11 FOR NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) UNRESPONSIVE TO BACILLUS CALMETTE-GUERIN (BCG) Bernard H. Bochner, Muneeb Alam, Juan C. Osorio, Jeffrey L. Wong, David Knorr, Lucas Blanchard, Juan Angulo-Lozano, Karissa Whiting, Venkatraman E. Seshan, Timothy Donahue, Eugene Cha, Alvin Goh, Robert Smith, Guido Dalbagni, Christian Hernandez, Melissa McCarter, Eugene J. Pietzak, Jonathan E. Rosenberg, and Jeffrey V. Ravetch Bernard H. BochnerBernard H. Bochner , Muneeb AlamMuneeb Alam , Juan C. OsorioJuan C. Osorio , Jeffrey L. WongJeffrey L. Wong , David KnorrDavid Knorr , Lucas BlanchardLucas Blanchard , Juan Angulo-LozanoJuan Angulo-Lozano , Karissa WhitingKarissa Whiting , Venkatraman E. SeshanVenkatraman E. Seshan , Timothy DonahueTimothy Donahue , Eugene ChaEugene Cha , Alvin GohAlvin Goh , Robert SmithRobert Smith , Guido DalbagniGuido Dalbagni , Christian HernandezChristian Hernandez , Melissa McCarterMelissa McCarter , Eugene J. PietzakEugene J. Pietzak , Jonathan E. RosenbergJonathan E. Rosenberg , and Jeffrey V. RavetchJeffrey V. Ravetch View All Author Informationhttps://doi.org/10.1097/01.JU.0001008640.01272.9d.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 2141-V11 is a novel anti-CD40 antibody developed by our group with enhanced binding to FcγRIIB resulting in effective tumor-specific T-cell responses in vivo. In preclinical bladder cancer models, including BCG-unresponsive disease, intravesical 2141-V11 results in durable anti-tumor immunity without systemic toxicity. Based on these findings, we initiated a first in human Phase I/II study of intravesical 2141-V11 for the treatment of BCG-unresponsive NMIBC. METHODS: This is an investigator-initiated Phase I, open-label, dose-escalation study to evaluate the safety and tolerability of intravesical 2141-V11 in patients with BCG-unresponsive NMIBC who are ineligible for or decline radical cystectomy (NCT05126472) (N=25). Following complete transurethral resection, intravesical 2141-V11 is administered once weekly for 3 doses with retreatment eligibility at week 13 and 25, depending on disease state. Dose escalation follows an MCRM design (Figure 1). Primary endpoints are safety and dose tolerability to determine maximal tolerated dose (MTD) and/or recommended Phase II dose. Secondary endpoints include pharmacokinetics and preliminary evaluation of clinical activity. Exploratory aims include investigation of biological markers of drug activity in tissue and urine. RESULTS: A total of 18 patients were enrolled by the data cutoff 11/2/23. Patients included had carcinoma in situ (CIS) with or without Ta/T1 (N=12) or Ta/T1 without CIS (N=6). Eight patients had a prior history of T1 disease. Patients received a mean of 12.7 doses of prior BCG. Intravesical 2141-V11 was well tolerated (no grade ≥3 events) with no dose-limiting toxicities up to the highest tested dose of 70 mg. MTD was not reached. Complete responses were observed at 3 and 6 months with final therapeutic analysis pending completion of follow up. Post-treatment urine studies reveal increased neutrophils/neutrophil-related cytokines, particularly in responders. Single-cell spatial phenotyping is ongoing. CONCLUSIONS: Intravesical 2141-V11 is well tolerated up to 70 mg with minimal local side effects and no evidence of systemic toxicity. Completion of accrual and biological correlatives will reveal on-target activity and early efficacy data. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e247 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Bernard H. Bochner More articles by this author Muneeb Alam More articles by this author Juan C. Osorio More articles by this author Jeffrey L. Wong More articles by this author David Knorr More articles by this author Lucas Blanchard More articles by this author Juan Angulo-Lozano More articles by this author Karissa Whiting More articles by this author Venkatraman E. Seshan More articles by this author Timothy Donahue More articles by this author Eugene Cha More articles by this author Alvin Goh More articles by this author Robert Smith More articles by this author Guido Dalbagni More articles by this author Christian Hernandez More articles by this author Melissa McCarter More articles by this author Eugene J. Pietzak More articles by this author Jonathan E. Rosenberg More articles by this author Jeffrey V. Ravetch More articles by this author Expand All Advertisement PDF downloadLoading ...