The past couple of months, some compelling new stories have circulated about promising Melanoma treatments. In June, you read about “ipi” – in the news and here on Melanoma Updates. And, this past month, more news touted early clinical trials with another targeted therapy drug, PLX4032. As always, we are cautiously optimistic, but to shed some light on two exciting, but still emerging options, I thought a basic overview might be helpful.

So, what do these drugs do? Quite simply, one attacks a gene mutation found in about 50% of all melanoma patients. And one works to modulate the immune system.

Ipi for Immunity

Ipi is an immune therapy drug: it tries to activate or stimulate the immune system to clear cancer cells. With the usual current immuno-therapy treatments, such as interleukin, we haven’t been able to significantly extend the immune response to melanoma cells. But Ipi has been shown to extend that immune protection for longer and longer time spans, for the first time ever, leading to 2-year survival rates in around 56% of a certain group of patients (again, with advanced melanoma survival rates typically not extending past 10 months.) Ipi has been in advanced trials for years, and the very promising Phase III results spurred the recent media frenzy. As such, it is on the fast track for priority approval – perhaps as soon as the end of this year – and may become the first new melanoma drug approved in decades.

Gene Mutation Therapy

First, it’s important to know that about half of patients with metastatic melanoma have a mutation in a gene called BRAF. This is a gene that seems to program the “runaway cell division that is a hallmark of cancer.” When the impact of the BRAF gene mutation was established, scientists set to work to find a way to switch it off or slow down the programming to cells, and one of those ways may be an exciting new gene therapy drug, PLX4032 (no catchy name as of yet.) A remarkable 81% of cases showed marked and in many cases immediate improvement and reduction in tumor size and growth. Granted, the news came after just a small Phase I clinical trial, but there was such excitement about the results that in a rare move, the drug has skipped Phase II and is now being tested in longer term and wider scope Phase III trials.

As reported in USA Today:

No other drug has ever helped that high a percentage of patients with melanoma or any other solid tumor, says Paul Chapman, co-author of the study in today’s New England Journal of Medicine. The results are especially striking, he says, considering that only 10% to 20% of patients respond to standard treatments for melanoma, which don’t improve overall survival.

USA Today also has a sidebar Q&A piece that does a nice job of summarizing the caution and optomisim surrounding PLX4032. They include a phone number for more information about it as well: 888-662-6728.

A One-Two Punch?

Since the back to back encouraging news broke for ipi and PLX4032, some are combining the two in other drug therapy trials. Here is a quote from the National Cancer Institute Bulletin this past week:

In June, researchers announced that ipilimumab, a treatment that targets the immune system, helped patients with advanced melanoma live longer. Together, ipilimumab and PLX4032 have changed the landscape of melanoma research and raised the prospect that the new agents could be tested in combination or sequentially, said Dr. Claudio Dansky Ullmann, who oversees melanoma trials for the NCI Cancer Therapy Evaluation Program.

"These studies have opened the doors to a lot of possibilities for treating metastatic melanoma,” said Dr. Dansky Ullmann. "We can now test many treatments that were not available or proven until recently. This area of research is taking off.”