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ComboMATCH Precision Medicine Clinical Trials

Illustration of strand of DNA rising from test tubes

The ComboMATCH trials will assign people with cancer to combination therapies based on the genetic characteristics of their tumors.

Credit: iStock

About ComboMATCH

ComboMATCH (Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice) is a group of precision medicine cancer clinical trials, including a registration trial and numerous treatment clinical trials. In the registration trial, people with cancer will have their tumors tested to determine what genetic changes are present and may be assigned to receive treatment based on those genetic changes. The trials seek to determine whether treating cancer with combinations of drugs targeting these specific genetic changes is effective.

Several treatment trials are open at any given time, each enrolling people whose tumors have the targeted genetic profile. Some ComboMATCH treatment trials will study different groups of people with the same genetic profile. Participants may be randomly assigned to compare outcomes in those treated with a drug combination versus people treated with just one of the drugs in that combination.

The drugs included in the trials have either been approved by the Food and Drug Administration (FDA) for specific cancers or are still being tested in other clinical trials but have shown some effectiveness against tumors with a particular genetic change.

Types of cancers studied

Some ComboMATCH treatment trials will test combinations of drugs based on specific changes in cancer cells no matter where the cancer is located in the body, whereas others will require that a participant's cancer started in a specific part of the body. You may be eligible to participate if you have a locally advanced or metastatic solid tumor with measurable disease and a targeted genetic change. In addition, your cancer must have progressed after you received at least one line of standard systemic therapy or if standard treatment has not been shown to prolong overall survival for people with your type of cancer.

How to enroll in ComboMATCH

You may join ComboMATCH by following these steps:

  • Potential participants must be under the care of an oncologist at a participating ComboMATCH site. Nearly 1,000 sites in the United States and Puerto Rico will participate. If you are not being treated at one of these sites, your oncologist can refer you to a participating site. See the protocol summary for a complete list.
  • Your oncologist must order routine gene testing of your tumor from a participating testing lab.
  • If your oncologist determines, based on the tumor test, that you might be eligible for ComboMATCH, the next step is to join the ComboMATCH registration trial and submit eligibility information.
  • Researchers with the registration study will use the clinical and genetic information submitted by your oncologist to determine if you are eligible for a ComboMATCH treatment trial, and if so, they will assign you to one.
  • Once enrolled in a treatment trial, you will be treated with the targeted drugs until the cancer begins growing again, the side effects become too bad, or treatment is completed.

For more information about the referral process and participating labs, visit Genomic Testing and the Laboratory Referral Process.

Goals of ComboMATCH

The primary goal for ComboMATCH is to see whether the use of drug combinations can overcome the resistance to treatment that can arise with the use of a single drug that targets a genetic change. The combinations that will be tested in ComboMATCH will typically use either two genetically targeted agents or one targeted agent along with a chemotherapy drug. Each drug combination tested in ComboMATCH was selected based on strong evidence of its promise to improve patient outcomes.

Treatment arms that are open and enrolling patients

ComboMATCH will include numerous treatment trials, or study arms. Some treatment arms are for any type of tumor with the targeted genetic change, whereas others may be only for specific tumor types. The following treatment trials are currently open and recruiting patients. Other ComboMATCH treatment trials will be added to the table below as they open to recruitment.

ComboMATCH Trials Recruiting Patients
Arm     Targeted genetic change     Drug(s) Cancer type
EAY191-S3 Activating AKT mutation Ipatasertib and paclitaxel Solid tumors
EAY191-N2 NF1 nonsense or frameshift mutations or NF1 gene deletion Binimetinib and fulvestrant Hormone receptor-positive, HER2-negative metastatic breast cancer
EAY191-N4 RAS pathway mutation Selumetinib and olaparib Ovarian or endometrial cancer
EAY191-A6 MAPK pathway mutations Binimetinib and chemotherapy   Previously treated advanced biliary cancer
EAY191-A3 RAS pathway mutation Palbociclib and binimetinib Ovarian, pancreatic, and other solid tumors
EAY191-E5 KRAS G12C mutation Sotorasib and panitumumab Advanced solid tumors
EAY101-N5 HER2 amplification Neratinib and palbociclib Solid tumors

From NCI-MATCH to ComboMATCH and beyond

ComboMATCH is a successor to the landmark NCI-MATCH precision medicine clinical trial. NCI-MATCH was one of the first large-scale clinical trials to match people who have cancer with treatment based on genetic changes in their tumor rather than their type of cancer. The trial showed that targeting genetic changes in a tumor may be an effective way to treat cancer. NCI-MATCH also demonstrated that people with advanced cancer may benefit from genomic sequencing to help plan their treatment. 

The information learned and infrastructure created for NCI-MATCH led not just to ComboMATCH but also to two additional new precision medicine trials: 

  • MyeloMATCH will test treatments based on genetic changes in the cancer cells of people with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). These cancers were not included in NCI-MATCH. 
  • immunoMATCH (iMATCH) will study how the immune status of a tumor affects the response to targeted treatments with immunotherapy.

As researchers learn more about matching people with treatment based on the genetic changes in their tumors, we will continue to make progress against cancer.

Trial collaborators

ComboMATCH is supported by NCI and is coordinated by the ECOG-ACRIN Cancer Research Group. Personnel from NCI, ECOG-ACRIN, and the other U.S. trial groups in NCI's National Clinical Trials Network (NCTN)—the Alliance for Clinical Trials in Oncology, NRG Oncology Group, the SWOG Cancer Research Network, and the Children’s Oncology Group— collaborated to develop ComboMATCH. 

In addition to NCTN groups, ComboMATCH will be open to all institutions and sites that participate in the NCI Community Oncology Research Program (NCORP).

The ComboMATCH registration trial is also identified as EAY191 and as NCT05564377.

Learn more about ComboMATCH

To learn more about ComboMATCH, speak with your doctor or health care team. More details about the ComboMATCH registration trial are available in the protocol summary.

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