MRD is shifting from prognostic marker to intervention trigger in oncology trials, influencing relapse risk, treatment escalation/de-escalation, and endpoints across tumor types including breast, colorectal, head & neck cancers, and hematologic malignancies.
FDA draft guidance supports MRD negativity (with complete response) as a surrogate endpoint for accelerated approvals in multiple myeloma, preferring randomized trials with completed enrollment before analysis.
Oncologic Drugs Advisory Committee (ODAC) unanimously voted 12-0 in April 2024 to endorse MRD for accelerated approvals due to its correlation with PFS and OS.
Key design considerations include aligning assay turnaround with clinical decisions, predefined escalation/de-escalation pathways, operational feasibility, and statistical models for longitudinal MRD data.
Experts emphasize intentional protocol integration of MRD for adaptive trials, preserving flexibility while maintaining traditional survival endpoints.