Lab Plays Central Role in Groundbreaking National Clinical Trial in Precision Medicine

By Frank Blanchard, Staff Writer
Studio portrait of Mickey Williams.

Mickey Williams, director, Molecular Characterization Laboratory. File photo. 

The Molecular Characterization Laboratory lies at the heart of an ambitious new approach for testing cancer drugs that will use the newest tools of precision medicine to select the best treatment for individual patients based on the genetic makeup of their tumors.

The protocol, called NCI-Molecular Analysis for Therapy Choice (NCI-MATCH), will start with tumor biopsies from as many as 3,000 patients to see if they have genetic defects for which a targeted cancer drug is available. Cancers will be treated based on their genetic profiles rather than by their location in the body, which is the conventional approach.

“NCI-MATCH is a unique, groundbreaking trial,” NCI Acting Director Doug Lowy, M.D., said in a news release announcing the program. “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,” Lowy said. “It holds the potential to transform cancer care.”

NCI-MATCH assay support will be coordinated through the Molecular Characterization Laboratory and three other laboratories around the country through a series of research subcontracts from Leidos Biomed. The other sites are at the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and the Yale Cancer Center.

The NCI-MATCH trial opened August 17 as described in an article by Barbara Conley, M.D., associate director, Cancer Diagnosis Program, NCI Division of Cancer Treatment and Diagnosis. In its first week, the trial enrolled 18 patients. Patient enrollments are continuing at sites around the country.

Mickey Williams, Ph.D., director of the Molecular Characterization Laboratory, said the next-generation sequencing assay that is used for the study will sequence 143 genes, including more than 6,044 gene-sequence variations that contain primary drivers for virtually every type of solid tumor and lymphoma.

The assay will detect DNA and RNA mutations, as well as gene amplifications and fusions, all of which offer potential targets for therapy.

The assay was analytically validated in extensive testing at the four labs to ensure consistent results, and it was vetted by the U.S. Food and Drug Administration (FDA) for use in the clinical study. The labs will have a turnaround time of about two weeks, which is critical for ensuring that the molecular information derived from tumors is current and reflects any changes that have occurred over time.NCI-MATCH graphic

In her article, Conley noted that the trial will accept patients with rare malignancies, those for which it would be almost impossible to mount a dedicated clinical trial otherwise. “Such patients include, for example, those with rarer lymphomas or with tumors of the salivary gland, skin appendages, various sarcomas, as well as patients with rare driver mutations in ‘common’ tumors (lung, breast, prostate, colon).”

About 2,400 clinical sites nationwide will be available to collect patient biopsies and treat patients. These sites are all part of NCI’s National Clinical Trials Network and the NCI Community Oncology Research Program, a successor to the NCI Community Cancer Centers Program. NCI-MATCH is supported by NCI and is coordinated by the ECOG-ACRIN Cancer Research Group, which was formed by the merger of the Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN).

“These sites are large and small, and all over the country,” Williams said. “This will afford patients living in [small] communities, where over 80 percent of cancer patients are treated, to have the same opportunities as patients that live near or can afford to travel to the larger cancer centers, like MD Anderson in Houston.”

To qualify for admission, patients must have disease progression after the current standard of care for their disease or have a cancer for which no standard of care exists. Patient tumor profiles will be matched against about 25 drugs that have either been approved by the FDA for treating patients, or are still experimental but have demonstrated effectiveness in early testing against tumors. As new drugs become available, they can be added to the trial.

Sequencing results are uploaded to the NCI-MATCHbox computer server in Bethesda for analysis by its rules-based software to determine which drugs would be right for which patients. Brent Coffey, director of biomedical informatics, Center for Biomedical Informatics and Information Technology, Frederick National Lab, led development of the software, which takes genetic information extracted from the patient samples, scans the information for mutations for which drugs are available, and recommends a course of treatment. These choices are reviewed by doctors.

NCI-MATCHbox also monitors each patient throughout the course of the clinical trial, Coffey said. While the software was designed to support NCI-MATCH, it has the potential to support future adaptive clinical trials in many research areas.

Photo caption: Infographic obtained from the NCI-MATCH website.