Given that many patients quickly develop resistance to single drugs, ComboMATCH comprises phase II treatment trials that will each evaluate a drug combination -- usually either two targeted drugs, or a targeted drug plus a chemotherapy drug. Some trials will include patients with specific changes in their cancer cells no matter where the cancer arose, whereas others will enroll patients with specific cancer types. Others will include children with cancer.

The drug combinations will include both U.S. Food and Drug Administration (FDA)-approved drugs and investigational substances from pharmaceutical companies. Since many thousands of potential drug combinations exist, researchers hope the initiative will help narrow down and prioritize the most promising ones.

One strength of the study is that the combinations being evaluated in ComboMATCH -- a collaboration among NCI and all five U.S. clinical trial groups within NCI's National Clinical Trials Network (NCTN) -- will be based on preclinical data showing that the combination is indeed better than either agent alone. Agreement among all NCTN representatives will be required to evaluate each combination.

In recent years, genomic testing of tumors has become standard for many types of cancer. In order for patients with locally advanced or metastatic solid tumors to be identified for possible enrollment in ComboMATCH, a doctor at any participating hospital or cancer center can refer them for eligibility screening if their test results show that they have a particular alteration being investigated in one of the trials. Any of the nearly 35 designated commercial and academic labs conducting standard of care genomic testing can also identify eligible patients.

Patients matched to a trial will be asked to provide a pretreatment tumor biopsy specimen for genomic profiling, enabling ComboMATCH investigators to later investigate why some treatments worked and others didn't. Three ComboMATCH trials are already open for enrollment for patients with specific mutations. More will be available in the coming months. NCI plans for ComboMATCH to eventually include about 2,000 patients.

"The majority of treatments that patients get nowadays are not genomically determined," Dr. James H. Doroshow, director of NCI's Division of Cancer Treatment and Diagnosis, said in a statement. "With ComboMATCH, we're trying to show that genomic abnormalities can be used to determine the most effective treatment combinations for patients."

"With ComboMATCH, we're hoping that by attacking both the genetic driver and the mechanisms of resistance, we will obtain more durable clinical responses and more benefit to patients," Dr. Jeffrey Moscow, of the Investigational Drug Branch in NCI's Division of Cancer Treatment and Diagnosis, added in a statement.