Interim analysis of a phase I dose escalation trial of the antibody drug conjugate (ADC) AGS15E (ASG-15ME) in patients (Pts) with metastatic urothelial cancer (mUC)

Abstract

Background: SLITRK6 is a protein highly expressed on bladder cancer cells. ASG-15ME is an ADC that delivers a small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), to tumors expressing SLITRK6. Methods: mUC pts previously treated with ≥ 1 prior chemo were enrolled using a modified continual reassessment method design. Slitrk6 expression was determined by immunohistochemistry (IHC). Disease assessments were performed every 8 weeks (wks) using RECIST v 1.1. ASG-15ME was administered IV wkly for 3 out of every 4 wks until no further benefit. Six dose levels were studied: 0.1, 0.25, 0.5, 0.75, 1, and 1.25 mg/kg. Results: As of 5/2/16, 51 pts were enrolled. 93% were SLITRK6 positive. Median age was 64 yrs; 100% were ECOG PS ≤ 1; 26 pts (52%) had ≥ 2 prior therapies (tx). Of 42 evaluable pts at doses considered active (doses ≥0.5 mg/kg), 1 has a complete response (CR) currently at 39 wks and 13 had a partial response (PR) (ORR =33%), including 4/ 11 pts (36%) with liver metastases and 5/12 pts (42%) who failed checkpoint inhibitor (CPI) tx. Median duration on ASG-15ME is currently 13 wks. Median progression free survival and duration of response are 16 and 15 wks, respectively. 42 pts (91%) had adverse events (AEs). The most common tx-related AE was fatigue (44%). 23 pts (50%) had Grade (G) 3/4 AEs, 9 (20%) of which were considered related. Ten pts had