Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study.

297 Background: Metastatic urothelial bladder cancer (UBC) is a mutationally-complex disease in which PD-L1 expression in the tumor microenvironment may inhibit immune-mediated antitumor responses. MPDL3280A is a PD-L1-targeting antibody with an engineered Fc domain that disrupts PD-L1/PD-1 and PD-L1/B7.1 signaling. Methods: MPDL3280A was studied in a phase Ia metastatic UBC expansion cohort. UBC pts received MPDL3280A 15 mg/kg IV q3w for ≤16 cycles. Efficacy-evaluable pts were dosed by January 27, 2014 (≥12 week follow-up) with a data cutoff of April 21, 2014. RECIST v1.1 was used to assess ORR. PD-L1 expression (by immune cell IHC) was centrally evaluated from archival biopsies. In-tumor gene expression and peripheral biomarker analyses were done on pts dosed by Nov 20, 2013, with a cutoff of January 1, 2014. Results: In the UBC cohort, 33 IHC 2/3 pts, 36 IHC 0/1 pts, and 1 PD-L1 pt with unknown IHC were efficacy-evaluable. Median pt age was 65 y (36-89), and 73% were male. Visceral and liver metastases...