By Lori Solomon, Editor, Diagnostic Testing & Emerging Technologies
The precision medicine trial NCI-MATCH (National Cancer Institute-Molecular Analysis for Therapy Choice) will open for patient enrollment in July. The multicenter trial will evaluate the effectiveness of targeted therapies based on genetic mutations, regardless of a patients’ cancer type. NCI-MATCH will assess, in parallel, more than 20 different study drugs or drug combinations, each targeting a specific gene mutation.
"[NCI-MATCH] is the first study in oncology that incorporates all of the tenets of precision medicine," said Doug Lowy, M.D., NCI acting director, in a statement. "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.”
An estimated 3,000 patients will have tumor samples sequenced with 1,000 expected to enroll across the individual drug substudies or targeted treatment arms. Large numbers of patient tumors will need to be screened, the investigators say, because most gene mutations occur in 10 percent or less of cancer patients. Most patients are expected to have one, or possibly two, treatable mutations.
The NCI Molecular Characterization Laboratory (Frederick, Md.) developed a sequencing-based test that examines 143 actionable gene mutations associated with cancer. Processing of all biopsy specimens occurs at the ECOG-ACRIN Central Biorepository and Pathology Facility at the University of Texas MD Anderson Cancer Center (Houston) for quality control. Sequencing analysis will be performed at four facilities using a standardized process. Pilot testing across the four locations showed "remarkable reproducibility" of the molecular results.
Ten treatment arms will initially launch in July, with the addition of at least 10 more arms expected within a few months. The 2,400 sites of the National Clinical Trials Network will enroll the patients. Patients will be treated with a targeted therapy matched to their tumor’s mutation for as long as their tumor shrinks or remains stable. A mix of U.S. Food and Drug Administration-approved drugs and investigational agents will be utilized.
Eligible patients are adults with solid tumors or lymphomas that have failed to respond to at least one line of standard systemic therapy, or with tumors for which there is no standard treatment. Patients with mutations that can be treated with a drug already approved by the FDA for their indication will not be eligible to use the same drug in NCI-MATCH, but secondary mutations matched to targeted treatments are eligible. At least one-quarter of enrollees are designated for rare cancers. Overall response rate and six-month progression-free survival will be assessed.
“For our purposes, a response rate of five percent or less in a molecularly-defined population will not be considered promising, whereas a response rate of 16 percent to 25 percent will be encouraging,” said NCI study co-chair Barbara A. Conley, M.D., in a statement. “After starting treatment in NCI-MATCH, a six-month progression-free survival of 15 percent will not be considered promising, whereas a progression-free survival at six months of 35 percent will indicate that we would want to develop that treatment further.”