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FINDING CURES TOGETHER<sup>SM</sup>

Investigational PD-L1–targeted Immunotherapy Safe for Patients With Triple-negative Breast Cancer, Effective in Some

4/20/2015

PHILADELPHIA — The investigational immunotherapy MPDL3280A was safe, tolerable, and showed early signs of durable clinical activity in patients with metastatic triple-negative breast cancer, according to data from a first-in-human phase I clinical trial presented here at the AACR Annual Meeting 2015, April 18-22.

“The emergence of approaches for harnessing the immune system to fight cancer is creating a lot of excitement for oncologists and immunologists because many of the responses that are being achieved are prolonged,” said Leisha A. Emens, MD, PhD, Johns Hopkins associate professor of oncology and member of the Cancer Immunology and the Breast and Ovarian Cancer Programs at the Johns Hopkins Kimmel Cancer Center in Baltimore. Leisha A. Emens, MD, PhD

“The latest analysis of our data revealed a 24-week progression-free survival rate of 27 percent, with an objective response rate of 19 percent, and three of four responses are ongoing,” continued Emens. “This is very exciting because longer responses are not typical of what occurs when patients with metastatic triple-negative breast cancer are treated with chemotherapy, which is the standard of care for this population. However, we need to validate these findings in larger cohorts of patients.”

Emens explained that the immunotherapy MPDL3280A is a type of drug called a biologic, specifically a monoclonal antibody, and that it blocks the interaction between a protein called PD-L1 and one called PD-1, which is found on T cells (a type of immune cell). She said that normally this interaction shuts off the ability of T cells to attack cancers and that blocking the interaction with MPDL3280A allows the T cells to once again eliminate tumor cells.

The phase I clinical trial is evaluating MPDL3280A as a potential treatment for a variety of advanced solid tumors. Emens and colleagues enrolled 54 patients with metastatic triple-negative breast cancer in the study, 69 percent of whom had PD-L1 on 5 percent or more of immune cells infiltrating samples of their tumors and were considered to have PD-L1–positive disease. Twenty-one of these PD-L1-positive patients could be assessed for signs of clinical activity.

Of the 54 patients (both PD-L1–negative and PD-L1–positive) who could be assessed for side effects, 63 percent experienced at least one drug-related adverse event, with 11 percent experiencing at least one grade 3 event. One patient experienced a grade 4 event. The most common drug-related adverse events were fatigue, fever, nausea, and loss of appetite.

This study was funded by Genentech. Emens has received research funding from Genentech for another clinical trial and a research grant from Roche. She has also received research funding from Merck, EMD Serono, Amplimmune, and Maxcyte, and consulted for Vaccinex, Celgene, Aveo, and Bristol-Myers Squibb. Under a licensing agreement between Aduro Inc. and Johns Hopkins University, the university and Emens are entitled to milestone payments and royalty on sales of the GM-CSF-secreting breast cancer vaccine. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict-of-interest policies. Emens is a member of the CTGTAC Advisory Committee of the Food and Drug Administration.

Press registration for the AACR Annual Meeting 2015 is free to qualified journalists and public information officers.

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