Credit: Argonne National Laboratory's

Tests of tumor samples taken before and after treatment with an experimental melanoma pill helped researchers find the right dose in early stage testing, an approach that may boost the drug's chances of success and aid in developing others, company researchers said on Tuesday.

Plexxikon's drug PLX4032 has already proven its prowess in an early clinical trial of melanoma patients, shrinking advanced melanoma tumors in 81 percent of 32 patients with the deadly and hard-to-treat skin cancer.

Looking at the biopsies from patients before treatment and two weeks after, we show we can inhibit the target directly in the tumor, said Gideon Bollag of the California-based biotechnology company, whose study appears in the journal Nature.

He said the drug had to almost completely block a chemical pathway in the tumor cells to reduce the size of the tumors in the melanoma patients.

Perhaps most surprisingly and interestingly, we needed to inhibit the target almost completely in order to demonstrate tumor shrinkage in the melanomas of the patients.

Bollag said companies increasingly are looking at how drugs change the molecular structure of tumors. Doing so can prevent costly failures in bigger clinical trials.

To understand exactly how compounds are working, it's really important to analyze the biopsies, Bollag said.

Now the company is working closely with Rocheto develop a companion diagnostic test that will help identify patients with what is called the BRAF mutation. These patients are the most likely to benefit from the compound.

The U.S. Food and Drug Administration has been working to streamline the process for validating and approving diagnostic tests that rely on markers in the body, such as a gene mutation or proteins in the blood.

We think this might be the first example where the therapy and the diagnostic go to the FDA at the same time, Bollag said.

Kathleen Glaub, Plexxikon's president, said the company is using a similar research approach in phase 1 trials of its other compound, which aims to treat cancers that have spread to the bone, including breast cancer.

I think all of us in this industry have to figure out different ways to develop drugs that are more efficient and enable us to move development faster, Glaub said in a telephone interview.

Plexxikon's drug, which is being co-developed by Roche, only works in the 50 to 60 percent of melanoma patients who have a specific mutation of the BRAF gene.

And its effects are brief. In only two cases the cancer has stayed away for at least a year, with the benefit to the others lasting about six months,

Unfortunately, the cancer cells eventually figure out how to rewire the signal in such a way that they bypass the action of the drug, Bollag said.

He said the company is trying to understand the tumor biology to see how to make the drug more effective, and they plan to combine it with other drugs to try to prolong the effect.

The first such trial will likely combine PLX4032 with a Roche drug called GDC-0973 that interferes with the MEK signaling pathway, which is also attacked by PLX4032.

Glaub said the company expects to present results of its phase 2 study in November at an international melanoma conference.