Verastem's ($VSTM) quest to develop drugs that block cell signaling pathways that cancer stem cells need to survive hits a major milestone in mid-2013, when it launches a 350-patient clinical trial of a potential companion biomarker test for its investigative mesothelioma drug treatment.
It is a major step for the Christoph Westphal-led enterprise, which debuted only in 2010 and raised $55 million in a 2012 IPO. And the company took some time to speak with FierceBiomarkers about its clinical trial plans.
"It's quite a big deal. The company is just three years old and we're about to launch a study that has potential for approval," chief medical officer Dr. Joanna Horobin said during a telephone interview from Tokyo. She's helping to build a clinical development strategy there for the biomarker test designed to be potentially paired with the company's investigative mesothelioma drug, VS-6063, a FAK inhibitor. Mesothelioma is a rare form of cancer that hits the lungs and can result from asbestos exposure.
LabCorp ($LH) partnered with Verastem on the companion test, which will be the focal point of a placebo-controlled, randomized multinational multicenter study that lasts for up to two years, with centers phased in over the next two years in the U.S., Australia, Western Europe (including the U.K. and the Netherlands), and in Japan toward the study's second half.
Researchers will be focusing their energies on merlin, a protein coded by the gene NF2 that suppresses tumors. And the idea of the immunohistochemistry test will be to test merlin levels in tumor samples, to determine which patients are merlin-negative, which might make them more likely to respond to VS-6063. Dan Paterson, the company's head of corporate development and diagnostics (also speaking with FMD from Tokyo), explains that between 40% and 50% of mesothelioma patients have low levels of merlin (which suppresses FAK), or no merlin at all.
The idea is to create randomized groups of patients with both high and low merlin levels, Verastem believes. While preclinical results suggest the drug works better in situations involving low merlin levels, the drug appears to have promise in both groups of patients, Paterson explains. At the halfway point, the adaptive trial will pause to make the decision to either go on with the trial for the whole group or only for patients with low or no merlin levels, based on the results they have at that point. If they narrow their option to patients with low merlin levels because the drug worked best for this class of patients, then the companion diagnostic becomes crucial to the drug's overall development.
"This is a potential companion diagnostic depending on the outcome of this study," Paterson explained. "We may or may not need a test but are partnered with LabCorp to do an analysis of the test, to make sure if we need to seek approval, that we can."
One drug exists on the market right now for mesothelioma--Eli Lilly's ($LLY) Pemetrexed, which can hold tumors in check for about half of patients. But the drug doesn't give them a complete response and then becomes toxic--most patients with mesothelioma face a near-certain death sentence. The goal with VS-6063 would be that the drug could be given after Pemetrexed loses effectiveness, serving as a second hit that could beat the tumors back and allow mesothelioma to become more of a chronic rather than fatal disease. Other companies are pursuing mesothelioma treatments, including Genelux (teamed with Memorial Sloan-Kettering Cancer Center) and GlaxoSmithKline ($GSK).