This morning at a meeting in Washington, D.C., researchers from the academia, the Food and Drug Administration, the National Cancer Institute, a leading patient advocacy group and several drug companies are describing a new clinical trial in lung cancer that could fundamentally change the way cancer drugs are studied and approved, speeding medicines that target specific genetic mutations in cancer toward the market and patients.
The study, dubbed “The Master Protocol,” aims to solve a fundamental problem of cancer research in the genomic age. Any one mutation that causes can be extremely rare, affecting perhaps one in 30 or even one in 100 patients. That makes studying a drug to hit that mutation incredibly tough. Sometimes hitting one mutation with one drug may not be enough, meaning that the patient whose cancer could be treated with a drug combination would be even rare.
That could swamp the already expensive process of conducting clinical trials. Researchers are used to searching through 14 patients before they found one patient to study in a clinical trial. Now they could have to perform a genetic test on ten times that number. Worse, each of the 139 patients who failed would then get other diagnostic tests to try to get them into other drug studies, meaning one patient could need hundreds of tests. Studying every drug one at a time, paired with one genetic test, becomes impossible. To make matters worse, many big cancer centers are already using new DNA-reading technology to test for cancer genes and trying to get patients access to drugs, but there is no organized system to track that data to find out if those experimental medicines work.
The situation is “untenable,” says Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Especially with personalized medicine we’re going to be seeing smaller patient numbers and its going to be hard for clinical trials to have access to patients even if they go worldwide.”
The Master Protocol offers a solution. The idea here is to have one over-arching plan (scientists call this a ‘protocol’) for studying lots of drugs. Instead of using one genetic test for each drug, they will use high-throughput DNA sequencing to scan tumors for 16 different genetic abnormalities that might be treated by as many as two dozen different drugs. Then patients will be put into separate studies for each new drug. Those for whom DNA sequencing doesn’t turn up a potential medicine will get a new type of immune system drug, known as a PD-1 or PDL1 inhibitor.
“It changes the idea of one test one drug,” says Roy Herbst, Chief of Medical Oncology, at Yale Cancer Center and the trial’s lead investigator. “That is the future, actually it is the present, it is just the way it has to be done.”
The study will not focus on all cancers, but on squamous cell lung cancer, a form that has proved particularly difficult to treat. Amgen AMGN -2.05%,AstraZeneca AZN -0.94%, and AstraZeneca’s MedImmune division have already signed on to provide drugs to the study. If they’re smart, other companies likeMerck , Pfizer PFE -0.19%, and Bristol-Myers Squibb will follow. Other studies have tried to examine multiple drugs at once, but this will be the first one aimed at getting the effective FDA approval.
That the FDA, NCI, and drug companies could all work together is in part because of the efforts of patient advocacy group Friends of Cancer Research and its charismatic leader, Ellen Sigal. She heard the idea discussed at a meeting her group runs with the Brookings Institution in D.C., and pushed for it. She personally called Herbst to help secure his involvement.
“It’s important for patients,” Sigal says. “They’re going to get state of the art treatment and they’ll get a better result. If you want to get to the bottom line, this is something patients can’t get on a one-off.” Says Pazdur: “This would not have proceeded without her.”
This trial could also be good new for Foundation Medicine, a startup focusing on cancer genetics that was backed by Google Ventures and Bill Gates and that recently raised $106 million in an initial public offering. Foundation was picked through a competitive bidding process to do the DNA sequencing for this study – a stamp of approval for the sequencing test it already markets to oncologists and patients and which delivered 2,577 patients in the most recent quarter. It also seems possible that the study results could help Foundation convince insurers and Medicare to pay for its test, which has a list price of $5,800. Right now Foundation is talking to Medicare and planning to start submitting bills to the agency by the end of the year.
“It’s really a catch-up to the genomic information that we’re providing to docs that is difficult to act on,” says Vincent Miller, a top oncologist who is now Foundation’s chief medical officer. “It’s not a theoretical exercise.”
The study is being described at a panel at Brookings at 10 a.m.