The Asco Post

ASCO 2013: Anti–PD-L1 Drug Shows Promising Anticancer Effects in a Variety of Advanced Cancers

By The ASCO Post
Posted: 5/17/2013 11:42:14 AM
Last Updated: 5/17/2013 11:42:14 AM

Key Points:
  • When treated with MPDL3280A, 21% of patients with locally advanced or metastatic solid tumors whose disease had progressed despite prior therapies experienced significant tumor shrinkage.
  • The highest number of therapy responses occurred in patients with lung cancer and melanoma.
  • Many patients reported improvement in their cancer-related symptoms, such as no longer requiring oxygen supplementation or decreased need for narcotics to control pain.

A phase I expansion study of the investigational drug MPDL3280A— an engineered PD-L1 targeted antibody—shows impressive tumor shrinkage rates in patients with several different cancers—including lung, melanoma, kidney, colorectal, and gastric cancers—that had progressed despite several prior treatments. The results will be presented at the 2013 ASCO Annual Meeting in Chicago (Abstract 3000).

About MPDL3280A

The new drug was safe and produced durable responses, with nearly all responses still ongoing. Several patients experienced tumor shrinkage within days of starting treatment. Importantly, many patients reported improvement in their cancer-related symptoms, such as no longer requiring oxygen supplementation or decreased need for narcotics to control pain.

PD-L1 is a protein frequently overexpressed on the surface of cancer cells that acts as a disguise, allowing cancer cells to hide from the immune system. When MPDL3280A attaches to the PD-L1 protein, the cancer can no longer hide from the patient’s immune system, allowing the body’s T cells to fight the cancer. MPDL3280A was specifically engineered for enhanced safety and efficacy compared to earlier PD-L1 or PD-1 targeted agents.

“We are impressed with the frequency and duration of the responses in these patients with very difficult-to-treat tumors. So far, almost none of the patients that have had tumor shrinkage have progressed,” said Roy S. Herbst, MD, PhD, Ensign Professor of Medicine at Yale Cancer Center and Chief of Medical Oncology at Smilow Cancer Hospital at Yale-New Haven. “This drug is part of an exciting new generation of drugs that unlock the power of the immune system to attack the cancer.”

Study Details

Efficacy was evaluated in 140 patients with locally advanced or metastatic solid tumors whose disease had progressed despite prior therapies. Tumor shrinkage was observed in patients with non–small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, and gastric cancer.

Overall, 29 out of 140 (21%) patients experienced significant tumor shrinkage and the highest number of therapy responses occurred in patients with lung cancer and melanoma. Therapy responses are still ongoing, with 26 out of 29 responders continuing to respond (time on study of responders = 3–15+ months).

It is not yet clear how PD-L1 expression affects response to MPDL3280A. Using an investigational diagnostic test, researchers analyzed archived tumor tissue from 103 patients and found that tumor shrinkage occurred in 36% of patients with PD-L1 positive tumors and, surprisingly, also in 13% of patients with PD-L1 negative tumors. The diagnostic test for PD-L1 is still evolving, so currently a negative result on the PD-L1 test could simply mean that tumors have less PD-L1 than the test currently detects.

Next Steps

This study has been expanded to include a larger range of solid tumors and blood cancers, with more than 275 patients currently enrolled. While these early data are encouraging, a randomized trial is needed to confirm the findings. A number of phase II and phase III studies are already planned to confirm the drug’s anticancer activity and further validate the utility of the PD-L1 diagnostic test. Researchers are also looking at ways it could be combined with other anticancer therapies to further boost responses over current standard treatments.

 “The fact that this drug was active in such a variety of tumors suggests that PD-L1 is part of a universally or generally important immune mechanism,” said ASCO President-Elect Clifford A. Hudis, MD. “Over the next few years, drugs that target and help activate and direct the immune system will likely take on a growing role in patient care, and it’s particularly exciting to see strong effects in patients whose cancer has progressed despite all other standard therapies.”

This study was supported by Genentech, Inc.

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®.

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