The trial seeks to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.
NCI-MATCH is a phase II trial with numerous small substudies (arms) for each treatment being investigated. It will open with approximately 10 substudies, moving to 20 or more within months.
The NCI-MATCH trial has two enrollment steps. Each patient will initially enroll for screening in which samples of their tumor will be removed (biopsied). The samples will undergo DNA sequencing to detect genetic abnormalities that may be driving tumor growth and might be targeted by one of a wide range of drugs being studied. If a molecular abnormality is detected for which there is a specific substudy available, to be accepted in NCI-MATCH patients will be further evaluated to determine if they meet the specific eligibility requirements within that arm. Once enrolled, patients will be treated with the targeted drug regimen for as long as their tumor shrinks or remains stable. Overall, trial investigators plan to screen about 3,000 patients during the full course of the NCI-MATCH trial to enroll about 1,000 patients in the various treatment arms.
Adults 18 years of age and older with solid tumors or lymphomas that have advanced following at least one line of standard systemic therapy, or with tumors for which there is no standard treatment, will be eligible. Each arm of the trial will enroll up to 35 patients. The trial’s design calls for at least a quarter of the 1,000-patients enrolled to involve people with rare types of cancer.
For several years now there has been much discussion of using targeted therapies to treat cancer—this will be the first big study to actually do it.
“NCI-MATCH is a unique, ground-breaking trial,” said Doug Lowy, M.D., NCI acting director. "It is the first study in oncology that incorporates all of the tenets of precision medicine. There are no other cancer clinical trials of this size and scope that truly bring the promise of targeted treatment to patients whose cancers have specific genetic abnormalities. It holds the potential to transform cancer care.”
Since many gene mutations in tumors are infrequent or unique, screening for individual mutations is not cost-effective or efficient in clinical trials. Instead, NCI-MATCH will use advanced gene sequencing techniques to screen for many molecular abnormalities at once. Large numbers of patient tumors will need to be screened because most gene mutations occur in 10 percent or less of cancer patients. Most patients are expected to have one, or at most two, treatable mutations in their tumors. By having multiple treatments available for these genetic abnormalities in a single clinical trial, several different study drugs or drug combinations can be evaluated simultaneously.
The cancer treatment drugs being used in NCI-MATCH include both U.S. Food and Drug Administration approved drugs as well as investigational agents that are being contributed by a number of pharmaceutical companies. Most of the arms in the trial will incorporate single-agent drugs that are either commercially available or are still being tested in clinical trials. However, a few arms will contain combinations of drugs for which there are enough safety data and evidence that they might be active against a particular genetic abnormality.
Screening has not started (starts in July 2015) and there is no specific timeline. Participants will continue to take the trial drugs until their cancer no longer responds to the medications. This approach may be the template for future targeted treatments. Specific drugs for specific gene mutations is a step forward. Watch for results—sometime soon, I hope.
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(c) 2012 Tom Beer and Larry Axmaker