NCI-MATCH pairs tumor mutations with matching drugs

volume 33 NumBeR 8 AuGuST 2015 nature biotechnology NCI’s division of cancer treatment and diagnosis. For example, 1–4% of all cancers have epidermal growth factor (EGFR) mutations that could be treated with Gilotrif (afatinib) a drug from Boehringer Ingelheim, which targets EGFR, approved in 2013 for non– small cell lung cancer. NCI-MATCH will be testing whether this is feasible. “Ordinarily, we’d need a zillion patients [for statistical accuracy], but the more drugs we have, the better chance that screening will find actionable mutations,” says Doroshow. Genomic tumor analysis has already been used in two other pioneering trials. Cancer Research UK launched the National Lung Matrix Trial in 2014 (Nat. Rev. Drug Disc. 13, 407, 2014), and the I-SPY2 trial in breast cancer (Nat. Biotechnol. 32, 117, 2014) began soon after, aiming to stratify patients umbrella” approach is conceived “very much in the thrust of President Obama’s Precision Medicine Initiative,” announced in January 2015, (Nat. Biotechnol. 33, 325, 2015). Flaherty is study chief and director of the Henri and Belinda Termeer Center for Targeted Therapies at the Massachusetts General Hospital Cancer Center and associate professor of medicine at Harvard Medical School, both in Boston. The study’s size and scope will allow researchers to screen many molecular abnormalities at once and may uncover infrequent gene mutations. These could make up to a quarter of all molecular alterations. “We are going after a large number of mutations with a very small frequency,” says James Doroshow, deputy director for clinical and translational research and director of the The National Cancer Institute (NCI) is launching a landmark clinical trial that will marry a tumor’s genetic profile with a treatment agent independent of its anatomical location. The NCI-MATCH (Molecular Analysis for Therapy Choice) trial will recruit at least 1,000 adults with advanced solid tumors and lymphomas that are either refractory to therapy or for which there is no standard therapy. The multi-arm phase 2 study trial will aim to identify ‘actionable mutations’ and explore whether drugs or drug combinations might be active against specific molecular abnormalities. “The MATCH trial is a truly innovative basket study that will allow us to determine if specific mutations are in fact drivers, and whether these tumors can then be treated with specific therapies,” said Roy Herbst, chief of medical oncology at the Yale Cancer Center in New Haven, and co-principal of the Lung Cancer Master Protocol (Nat. Biotechnol. 32, 116–118, 2014). NCI-MATCH will use a single DNA sequencing test to search for variants in 143 genes associated with cancer that can be matched with targeted drugs included in the trial. The study will include 20 different drugs that are either available commercially or are investigational agents donated by a number of companies, which are also contributing their expertise. Patient enrollment begins in July and will include 2,400 participating sites across the US. The ECOG-ACRIN (Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network) cancer research group, with headquarters in Philadelphia, is leading the study. The study will have multiple treatment arms with participants grouped by tumor mutation status. Medical oncologist Keith Flaherty says the trial’s “broad nCI-MATCH pairs tumor mutations with matching drugs