ComboMATCH Clinical Trial Protocol Updates Enhance Patient Care

Test tubes with liquid filled with red and blue colored DNA chromosome strands

In January 2026, important updates were added to ComboMATCH’s protocol and informed consent document. The updates make ComboMATCH uniquely poised to optimize its clinical trial screening efforts and the longer-term treatment options for patients enrolled on the trial.

ComboMATCH, a successor trial to the landmark NCI-MATCH precision medicine trial, is studying whether targeted combination therapies can provide clinical benefit to patients whose tumors have specific DNA aberrations. The study assesses whether the combination can overcome drug resistance in patients with specific molecular alterations based on evidence of synergy of the drug combinations in preclinical in vivo studies.

Using ctDNA for Patient Screening to Determine Trial Eligibility
Sequencing circulating tumor DNA (ctDNA) can now be used to non-invasively screen patients for ComboMATCH eligibility, instead of requiring a test result from tumor tissue. When a patient enrolls on the trial, they will still be asked to provide a fresh tumor biopsy for research purposes; however, if a fresh biopsy cannot be obtained (due to risk or lack of a biopsy site) archived tumor tissue from <1 year prior to enrollment can be used. If neither biopsy is available, the patient may still be enrolled. It remains important for the patient to donate blood for research which will be used for ctDNA analysis to study treatment response, assess tumor burden, and study drug resistance.

Returning Results of Progression Biopsies to Assist with Further Treatment
The trial’s correlative studies originally included sequencing the DNA from tumor tissue if the patient’s tumor progressed following treatment. Now the sequencing results obtained from those progression biopsies will be returned to the patient’s treating physician to help determine future treatment options for the patient following progression on the treatment trial. This effort is unique to ComboMATCH, as most precision medicine clinical trials do not provide this essential information to patients.

Learn more detailed information about the ComboMATCH study and see the list of treatment arms actively recruiting new patients.

ComboMATCH is supported by NCI and is coordinated by the ECOG-ACRIN Cancer Research Group.