ASCO 2014: Investigational Anti–PD-L1 Antibody Demonstrates Promising Activity in Certain Patients With Metastatic Bladder Cancer


Key Points

  • The anti–PD-L1 monoclonal antibody MPDL3280A had an overall response rate of 52% in patients with previously treated metastatic PD-L1–positive urothelial bladder cancer.
  • In patients who were PD-L1–negative, the overall response rate was 11%.
  • The FDA has granted MPDL3280A Breakthrough Therapy Designation in bladder cancer.

In a phase I study, the investigational anti–programmed death-ligand 1 (PD-L1) monoclonal antibody MPDL3280A demonstrated promising overall response rates in patients with previously treated metastatic urothelial bladder cancer whose tumors were characterized as PD-L1–positive. The results of the study were presented at the 2014 ASCO Annual Meeting in Chicago (Abstract 5011).

MPDL3280A is a monoclonal antibody designed to target PD-L1 and prevent it from binding to PD-1 and B7.1 on the surface of T cells, thus restoring the immune system’s ability to effectively detect and attack tumor cells. The FDA has granted Breakthrough Therapy Designation to MPDL3280A in bladder cancer.

Objective Responses in Half of PD-L1–Positive Patients

This single-arm, multicenter, open-label trial included 68 patients with previously treated, metastatic bladder, including 30 patients identified as PD-L1–positive by an investigational PD-L1 diagnostic test currently under development. Patients received MPDL3280A every three weeks for up to 1 year.

The median time to response was 42 days. After 6 weeks of follow-up, the objective response rate as measured by RECIST criteria was 43% in patients with PD-L1–positive patients; at 12 weeks, this increased to 52%. A complete response was observed in 7% of PD-L1–positive patients. In patients who were PD-L1–negative, the overall response rate was 11%.

Adverse events were consistent with what has been previously reported for MPDL3280A, and there were no severe (grade 4–5) treatment-related adverse events. The most common adverse events observed in more than 5% of patients were decreased appetite, fatigue, nausea, pyrexia, and asthenia.

Metastatic urothelial bladder cancer is associated with a poor prognosis and limited treatment options. The study results in advanced bladder cancer patients “point to a new era in cancer treatment for a disease that has not seen a major advancement since the introduction of cisplatin-based combination chemotherapy in the 1980s,” said senior author Daniel P. Petrylak, MD, Professor of Medicine and Urology at Yale Cancer Center and Yale School of Medicine.

The study was sponsored by Genentech. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.