Abstract CT064: Treatment for metastatic platinum-resistant urothelial cancer (PRUC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): phase I/II clinical experience
Authors: Tagawa Scott T. , Faltas Bishoy , Lam Elaine , Messersmith Wells A. , Saylor Philip , Bardia Aditya , Hajdenberg Julio J. , Morgans Alicia K. , Berlin Jordan D. , Lim Emerson , Kalinsky Kevin , Maliakal Pius , Sharkey Robert M. , Wilhelm Francois , Goldenberg David M. , Ocean Allyson J. 
Published: July 2016

Abstract
Background. Patients (pts) with PRUC have an aggressive disease with limited therapeutic options. Sacituzumab govitecan (IMMU-132) is an ADC comprised of SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized mAb. In vitro and in vivo preclinical data show that this is a unique ADC, with a high drug:antibody ratio of 7.6. It is capable of delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The ADC and mAb are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is elevated in most epithelial cancers (&gt;80%), including UC. The efficacy and safety of this new ADC is examined in PRUC pts.
Methods. A Phase I/II clinical trial (ClinicalTrials.gov, NCT01631552) is enrolling PRUC pts. IMMU-132 is administered on days 1 and 8 of 21-day treatment cycles. Treatment is continued based on tolerance or until progression, with safety and response assessments (RECIST 1.1) made every week and every 8 weeks, respectively.
Results. Fifteen PRUC pts were enrolled by 11/10/15 and 14 are evaluable [median age 68 yrs, 93% M, 71% with ECOG 1, 71% with visceral metastases], with a median of 2 (range, 1-5) prior chemotherapies. IMMU-132 doses given were 8 mg/kg (N = 3), 10 mg/kg (N = 10), or 12 mg/kg (N = 1).
Six patients have confirmed partial response, providing an objective tumor response rate of 46% in 13 patients assessable by RECIST 1.1. The clinical benefit ratio (PR+SD &gt; 4 months) is 57%. The current median progression-free survival (PFS) is 8.1 months with 50% maturity (# events divided by # patients), and median overall survival (OS) is 10.8 months, with 79% patients still alive.
Among collected adverse events so far among 15 UC pts enrolled before 8/31/15, grade 3+ drug-related toxicities above 5% incidence (single events) are neutropenia (9%), diarrhea (9%) and staphylococcal bacteremia (9%). No patient developed antibodies (by ELISA) to the antibody or drug.
Conclusion. Compared to historical response rates of &lt; 20% in this clinical setting, PFS of 2-4 mos, and OS of 4-9 mos for pts with PRUC, the early efficacy seen in this study to date combined with the toxicity profile encourage further study of IMMU-132 at the 10 mg/kg dosing level.
Citation Format: Scott T. Tagawa, Bishoy Faltas, Elaine Lam, Wells A. Messersmith, Philip Saylor, Aditya Bardia, Julio J. Hajdenberg, Alicia K. Morgans, Jordan D. Berlin, Emerson Lim, Kevin Kalinsky, Pius Maliakal, Robert M. Sharkey, Francois Wilhelm, David M. Goldenberg, Allyson J. Ocean. Treatment for metastatic platinum-resistant urothelial cancer (PRUC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): phase I/II clinical experience. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT064.