A multi-center phase I study using an investigational immune therapy drug has found that the presence of an immune-suppressing protein in non-cancerous immune cells may predict how patients with different types of cancer respond to treatment. The study, led by a Yale Cancer Center investigator, was published recently in the journal Nature.
The trial included patients with melanoma or cancers of the lung, kidney, colon, GI tract, or head and neck, whose tumors were evaluated for PD-L1 expression by a novel assay. PD-L1 is a protein expressed by many tumor types that is believed to act as a stop sign that prevents the immune system from attacking cancer cells. Patients were treated with MPDL3280A, a drug that blocks PD-L1 and is being developed by Genentech, a member of the Roche group.
The trial differed from other immune therapy trials in that it incorporated serial biopsies of patients before and during treatment to identify a tumor profile that predicts response to treatment, says the paper’s first author, Roy Herbst, PhD. “We can begin learning how to use combination therapies to affect the immune response cycle,” he adds. The serial biopsies revealed the characteristics of both functional and non-functional immune responses and provided a baseline for how patients respond and don’t respond to treatment.
Of the 175 patients enrolled, 21% showed partial or complete response to MPDL3280A, with some being rapid and durable. Across all tumor types, 46% of patients with high PD-L1 expression on non-tumor cells showed a partial or complete response. Also notable was the finding that smokers responded better to the drug than nonsmokers. This could provide more general insight into how smokers and nonsmokers respond differently to drugs. Read the article preview.
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