Researchers at UCLA’s Jonsson Comprehensive Cancer Center (JCCC) have reported promising results from treatment of two types of deadly cancers with a new drug known as MK-3475. It was found promising for the treatment of two types of cancer that, in most cases, have very low survival rates. The first is metastatic melanoma, a malignant skin cancer that metastasizes (spreads) aggressively beyond the initial tumor to invade other vital organs, such as brain, lungs or liver. The other is metastatic non-small cell lung cancer, which is responsible for the highest number of cancer deaths in the US each year. The findings were presented on June 3 at the American Society of Clinical Oncology (ASCO) Annual Meeting 2014 in Chicago by Dr. Antoni Ribas, professor of hematology-oncology and JCCC member.
MK-3475 is an antibody that targets a protein expressed by immune cells called PD-1. The protein acts as an immune checkpoint, which causes the immune system’s T cells to not recognize cancer cells as invaders. MK-3475 amps up the immune system; thus, allowing the T cells to identify and attack cancer cells. The Food and Drug Administration (FDA) granted a breakthrough therapy designation to MK-3475 for unresectable (unable to be surgically removed) or metastatic melanoma in May 2013 under its Accelerated Approval program.
The UCLA clinical trials have shown extraordinary treatment success with MK-3475 for melanoma and lung cancer. Dr. Ribas led what is probably the largest phase 1 study ever conducted in cancer; it comprised 411 patients who had metastatic melanoma. The cancer has an average five-year survival rate of less than 5%; the one-year overall survival rate is 69% for all patient subgroups. Response to the drug, documented by tumor shrinkage, was continuing in 88% of patients at the time the study was analyzed; this was after an average 12-month follow-up. Tumors responded in patients from all the different dose regimens and in various patient subgroups, including those whose cancers had exacerbated (worsened) after having received the drug ipilimumab. There are currently no treatment options with proven activity for those patients.
Dr. Ribas noted, “We are seeing unprecedented durable responses with this drug, MK-3475 is working in patients that had not been treated, as well as those who had been given ipilimumab and other therapies. These are early data, but response rates of this magnitude in such a large sample, with only four percent of patients discontinuing because of drug-related side effects, indicate the importance of moving forward quickly with this drug.” Overall, 34% of the patients responded to MK-3475, including 40% not treated with ipilimumab and 28% whose cancer exacerbate despite ipilimumab treatment. Treatment-related side effects were, in most cases, mild and reversible; 8% of patients experienced major side effects.
Dr. Edward Garon, assistant professor of hematology-oncology and JCCC member led a study comprised of 217 metastatic non-small cell lung cancer patients whose disease exacerbated during or after at least one prior therapy as part of the same MK-3475 study. He explained that this was the largest report of lung cancer patients being treated with this approach of inhibiting PD-1. The standard therapy for patients in this situation is single-drug chemotherapy. After one prior therapy, an overall survival of approximately six to nine months is the norm, with less than 10% of patients responding to therapy; even in those patients, the responses are generally short-lived. Outcomes are typically worse in patients who have received two or more therapies, which was often the case in this study. For the majority of lung cancer patients whose tumors expressed PD-L1, a target of PD-1, 23% responded to this therapy, and the responses were often long-lasting.
“We are very excited about the preliminary results we are seeing with MK-3475 in these advanced lung cancer patients,” noted Dr. Garon. He added, “It is a very well tolerated drug, so the benefits are enhanced by the fact that it generally has very little negative effect on patient quality of life. We are conducting additional trials with MK-3475, and based on our work, we hope the drug will soon be available to patients throughout the world.”