ComboMATCH Precision Medicine Clinical Trials
The Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH) initiative is the largest of its kind to test combinations of cancer drugs guided by tumor biology. The endeavor aims to identify promising treatments that can advance to larger, more definitive clinical trials outside of ComboMATCH. It comprises numerous phase 2 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 in the body, whereas others will enroll patients with specific cancer types.
ComboMATCH is a cross-group collaboration among NCI and all five U.S. clinical trial groups within the National Clinical Trials Network (NCTN). It is a successor to NCI-MATCH, the groundbreaking precision medicine clinical trial. In NCI-MATCH, people were assigned to treatment based on genetic changes in their tumor rather than their type of cancer. For the most part, NCI-MATCH evaluated single drugs targeting the mutation thought to be driving the growth of a patient’s tumor. However, many patients quickly developed resistance to these single drugs.
The combinations will include both U.S. Food and Drug Administration-approved drugs and investigational agents contributed by pharmaceutical companies. Hundreds of thousands of potential drug combinations exist, so one challenge has been to narrow down and prioritize the most promising ones.
There are several ways in which patients with locally advanced or metastatic solid tumors will be identified for possible participation in ComboMATCH. In recent years, genomic testing of tumors has become a standard part of care for people with many cancer types. A doctor at any of the community hospitals and cancer centers participating in ComboMATCH can refer their patient for additional eligibility screening if the patient’s test results show that they have a particular alteration being investigated in one of the treatment trials. Any one of the nearly 35 designated commercial and academic labs that are conducting genomic testing as part of standard of care can also identify patients who might be eligible for a ComboMATCH trial. Patients who are matched to a trial will be asked to provide a pretreatment tumor biopsy specimen for genomic profiling. This will enable ComboMATCH investigators to later probe other questions, such as why some treatments worked and others didn’t.
Four ComboMATCH trials are open for enrollment:
A study testing the use of fulvestrant (Faslodex) and binimetinib (Mektovi) in patients with an NF1 mutation in hormone receptor-positive breast cancer that has spread (NCT05554354)
A study testing the use of selumetinib (Koselugo) and olaparib (Lynparza) or selumetinib alone in women with a RAS mutation who have endometrial or ovarian cancer that has come back or persists despite treatment (NCT05554328)
A study of chemotherapy plus ipatasertib in patients with AKT mutations who have solid tumors that have spread (NCT05554380)
Six additional trials will be available in the coming months, with more to be added over time. Overall, there are plans for ComboMATCH to include about 2,000 patients, but that number could grow.
Unlike NCI-MATCH, which did not include children, but rather had a separate parallel trial called PediatricMATCH, some ComboMATCH trials will include children with cancer.
Two additional precision medicine cancer treatment trials will also be launched. ImmunoMATCH has started with a pilot study to determine how prospective characterization of the immune status of a tumor can be used to improve the response to targeted treatments using immunotherapy, with plans to expand into larger studies in the future. MyeloMATCH will test treatments based on genetic changes in the cancer cells of people with acute myeloid leukemia or myelodysplastic syndromes.
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
ComboMATCH Trials Recruiting 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.
Arm - Targeted genetic change - Drug(s) - Cancer type
EAY191-E4 - Taxane resistance - Nilotinib and paclitaxel - Solid tumors previously treated with a taxane
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
