ComboMATCH (EAY191)

ComboMATCH opened in April 2023 under ECOG-ACRIN with the same national machinery as NCI-MATCH but a different entry route: instead of a single central assay, patients can be registered on the strength of a genomic report from any NCI-designated laboratory, which removes the biopsy and turnaround delay that kept many NCI-MATCH patients from ever being assigned.

Each sub-study pairs a targeted drug with a second agent, chosen where patient-derived xenograft or other preclinical work showed the combination overcomes the resistance that defeated single agents, and several sub-studies are randomised against the single drug so that the contribution of the partner is measured rather than assumed. The registration protocol plans for close to 3,000 patients across the sub-studies.

Nothing has reported yet. What the trial is meant to change is the evidentiary standard for precision oncology: if matched combinations succeed where NCI-MATCH's single agents failed, the genotype-first approach survives in a new form; if they do not, the lesson will be that tissue and lineage matter more than the alteration list.