Clinicaltrials.gov identifier:
Sponsor:
MedImmune LLC
Enrollment:
1014
Study Design:
Phase I/II multicenter first in human study with standard 3+3 dose escalation in advanced solid tumors. The primary endpoint included safety and tolerability. The secondary endpoints include objective response rate, progression-free survival, overall survival, and PD-L1 expression on both tumor cells and tumor infiltrating immune cells.
Rationale:
This is a first in human study of Medimmune’s PD-L1 inhibitor durvalumab (MEDI4736) focused on dose expansion in a urothelial bladder cancer cohort (Massard C et al).
Comments:
Durvalumab had a reasonable safety profile and ORR was greater in the PD-L1+ group versus the PD-L1 negative group. Of note, each trial has used different definitions for PD-1/PD-L1 expression. Expression does appear to correlate with response with some tests but absolute numbers are variable across different agents and different studies. Phase III trials are ongoing with this agent in bladder cancer.
Results:
61 bladder cancer patients were enrolled. Drug-related adverse events occurred in 64% and only 3 patients had ≥grade 3 adverse events. Objective response rate (ORR) was greater in patients with at least 25% or greater PD-L1 expression in either tumor cells or tumor infiltrating immune cells versus less than 25% expression in both (46% vs. 0% ). ORR was 46% in the PDL-1 subgroup vs 0% in the PDL-1 negative group. For the whole population, the RR was 31% . Median duration of follow-up was26 weeks.
