Is it safe to say the age of immunotherapy in cancer treatment has arrived?
If so, it’s had a few sputtering starts and disappointments. The promise of training the body to recognize and kill cancer cells–without the damaging side effects of traditional cancer therapy–has intrigued us for years. But we now have a handful of immunotherapy drugs approved for cancer treatment, and many more on the horizon, it seems, from the studies released in anticipation of the annual meeting of the American Society of Clinical Oncology (ASCO).
Information released today in preparation of the meeting highlights several studies, including two new immunotherapy approaches for a variety of cancers, including melanoma.
Programmed Cell Death
The two studies zero in on the functions of a protein called PD-1 (programmed cell death 1), which lives on the surface of certain immune cells called T cells. In normal situations, T cells express PD-1 to down-regulate the immune system, preventing it from staging an over-the-top immune response to healthy cells. Ideally, T cells recognize and attack cancer cells.
However, cancer cells can be sneaky. And some cancer cells express a protein on their surface called PD-L1 (PD-ligand 1), which binds to T cells’ PD-1. Once they bind, the cancer cells become somewhat invisible to the immune system, evading recognition and death. Scientists have developed a new class of drugs that blocks this interaction.
An experimental drug called MPDL3280A (if it moves forward, it will ultimately receive a new name) binds to PD-L1 on cancer cells, which prevents it from binding to the T cell. In the study, patients with metastatic or incurable cancers, including melanoma, lung, kidney, head and neck, colorectal and gastric cancers, were given the antibody drug intravenously every three weeks.
Because it was a phase 1 study, the goal was to discover the highest, but safest dose. Because side effects were infrequent, a maximum tolerated dose was not found–which is a good thing. Moderate side effects seen during the trial included hyperglycemia, fatigue and increased liver enzymes.
An interesting note is that PD-L1 doesn’t occur in all cancers. Tumors that expressed PD-L1 responded more favorably to the drug, which may present an opportunity to use the protein as a biomarker for treatment. A third of patients who had PD-L1-positive tumors responded to MPDL3280A, as opposed to only 13 percent of patients with PD-L1-negative tumors. The duration of the response also appears favorable, with 26 of 29 responders still seeing benefit at their last appointment (which ranged from 3 to 15 months).
The study has been expanded to include even more cancer types and hematologic (blood) cancers. Randomized phase 2 and 3 studies are planned to confirm the drug’s activity and the diagnostic test for PD-L1. Additional studies include a phase 2 study in lung cancer and combining the drug with Zelboraf in a phase 2 melanoma study.