EAY191 - Molecular Analysis for Combination Therapy Choice (ComboMATCH)

By James M. Ford, MD

An amendment to the EAY191/ComboMATCH precision medicine initiative now adds another option for patients to be assigned to one of its treatment trials by permitting enrollment based on results from a liquid biopsy. This procedure tests for circulating tumor DNA (ctDNA) in the blood.

Additionally, the amendment enables DNA sequencing results obtained from progression biopsies to be returned to the patient and treating physician for consideration in determining a ComboMATCH participant’s future care.

Both provisions are included in Addendum #5, which was activated on January 22, 2026. Previously, only sequencing from tumor tissue was permitted. Now, potential treatment trial eligibility will be based on tumor tissue or ctDNA CLIA-compliant genomic report results from one of the initiative’s designated laboratories. (If both ctDNA and tumor testing results are available, both CLIA reports must be submitted).

Addendum #6, also activated on January 22, 2026, clarifies the Oncomine assay used to sequence and return results from the progression biopsy.

The EAY191/ComboMATCH initiative opened in 2023 as a platform for a series of phase 2 treatment trials to evaluate new combinations of anti-cancer drugs. The program is for adults and children with locally advanced or advanced solid tumors whose cancer progressed on at least one line of standard therapy or who have no standard treatment that has been shown to prolong overall survival.

Drug combinations are based on strong early evidence that they may be more effective than single therapy in treating some cancers. Participants are assigned to ComboMATCH treatment trials based on their genomic results. The drug combinations are either two targeted therapies given together or a targeted drug with chemotherapy. Each treatment trial has its own research goals, patient eligibility criteria, and enrollment timeline. Before assignment to a treatment trial, patients must be enrolled in the EAY191 registration trial.

Currently, three ComboMATCH treatment trials are recruiting patients:

• EAY191-E5 – sotorasib and panitumumab in solid tumor cancers with KRAS G12C mutation
• EAY191-N4 – selumetinib and olaparib in ovarian or endometrial cancer with a RAS pathway mutation
• EAY191-N5 – neratinib and palbociclib in HER2+ solid tumor cancers (except breast cancer)

The ComboMATCH study team is actively looking for new concepts based on combination treatments that preclinical data suggest have greater efficacy than monotherapy. The treatment trials can be randomized or single arm. ComboMATCH is a cross-network study, so members of any of the cooperative groups listed below may submit concepts for review and are encouraged to do so.

The ComboMATCH precision medicine initiative is led by the ECOG-ACRIN Cancer Research Group and the National Cancer Institute through the National Clinical Trials Network. ComboMATCH includes several treatment trials led by the Alliance for Clinical Trials in Oncology, Children’s Oncology Group, ECOG-ACRIN Cancer Research Group, NRG Oncology, and SWOG Cancer Research Network.

Learn more about EAY191/ComboMATCH at ecog-acrin.org.

Dr. Ford (Stanford Medicine) is the study chair for this trial.

The study co-chairs are Funda Meric-Bernstam, MD (The University of Texas/MD Anderson Cancer Center), Lyndsay N. Harris, MD (National Cancer Institute), and Alice P. Chen, MD (National Cancer Institute).