338 Background: Metastatic bladder cancer (mBC) is a fatal disease and novel therapies are urgently needed. Preclinical evidence suggests role of AR in BC progression. Enzalutamide (ENZ) is a novel AR antagonist that inhibits nuclear translocation of AR, DNA binding, and co activator recruitment. Our ongoing phase 1 trial is is assessing safety and tolerability of ENZ in combination with gemcitabine and cisplatin (GC) in mBC and explore novel correlatives in tumor tissues and CTCs. Methods: The study has 2 phases, dose escalation phase and dose expansion phase. The dose escalation phase had 2 cohorts testing ENZ at doses of 80 mg and 160 mg respectively with GC (gemcitabine 10000 mg/m2 on days 1 and 8 and cisplatin 70 mg/m2 on day 1 every 21 days). The dose escalation phase allowed both AR + and AR - mBC pts. Patients will be monitored for safety and tolerance with laboratory studies, clinical exam, and CT scans to assess response. Primary objective is safety and tolerability of ENZ and GC. Secondary objectives are objective tumor response, time to progression, and overall survival. Exploratory objectives include qualitative and quantitative evaluation of AR and pAKT expression with AQUA in tumor tissues and correlation with outcomes. CTCs are being evaluated at baseline and cycle 3, including AR expression in CTCs and correlation will be done with tumor AR expression and clinical outcomes. Key eligibility criteria are ECOG PS of 0-1, and no contraindications to study drugs. Results: In the dose expamnsion phase, 3 patients were enrolled in each cohort of 80 mg and 160 mg of ENZ respectively with GC and there were no DLTs or significant AEs related to the combination; the MTD of ENZ is 160 mg. Enrollment on dose expansion phase is ongoing. detectable CTCs were seen in 4/6 BC patients with 2 patients showing AR + CTCs at baseline. Further CTC analysis, including AR expression and tissue analysis for AR and pAKT analysis in tissues is ongoing. (Trial identifier: NCT02300610). Conclusions: This is a first of its kind clinical trial exploring the role of AR signaling in BC and targeting it with ENZ along with GC. The data gathered form this study will help us understand the clinical relevance of targeting AR in BC. Clinical trial information: NCT02300610.
376. Phase 1/2a, Dose-Escalation, Safety and Proof of Concept Study of Intravesical BC-819 in Patients with Superficial Bladder Cancer
