With mutation-driven therapies and advanced biomarkers shaping the future, AML trials now demand more speed, precision, and operational agility than ever before.
Sheridan, WY, 13 November 2025 – Acute myeloid leukemia (AML) is no longer viewed as a single condition. It is now understood as a group of genetically distinct subtypes, each with its own behaviors and treatment needs. This shift is changing how clinical trials are planned and run. To stay competitive, sponsors must adopt integrated biomarker workflows, flexible trial designs, and earlier use of real-world evidence.
Two key genetic alterations—KMT2A rearrangements and NPM1 mutations—are driving rapid progress in targeted therapies. This trend began with FLT3 inhibitors almost a decade ago and has accelerated with the development of menin inhibitors. Today, more than half of AML patients have a targetable mutation, pushing trials into a new phase that requires stronger collaboration, faster testing, and more precise planning.
Rethinking Combination Strategies in Modern AML Trials
Menin inhibitors show promise for patients with genetic alterations affecting HOXA9-MEIS pathways, including KMT2A, NPM1, and other fusions. While monotherapy has demonstrated clear benefits, resistance remains a challenge. Combining menin inhibitors with standard treatments or introducing them earlier may improve outcomes, but also adds complexity.
Key decisions dose sequencing, timing, and safety planning, directly affect feasibility. As Dr. Chris Keuker of Syneos Health notes, success depends on smart integration of these therapies into a broader treatment strategy.
Why Biomarker Testing Creates Enrollment Delays
AML progresses quickly, giving clinicians only a short window to identify eligible patients for trials. Many programs, however, lack real-time testing infrastructure and clear sample workflows. For trials targeting KMT2A or NPM1, delays between relapse diagnosis and enrollment can be costly.
Dr. Liat Vidal of Syneos Health emphasizes the need for repeat genetic testing, since mutations can evolve at relapse. Sponsors must secure diagnostic partnerships early, confirm lab capabilities, and embed biomarker workflows during feasibility, not after protocols are finalized.
The Need for Operational Agility
Mutation-driven studies are complex. They require tight coordination across clinical operations, regulatory teams, and data management. Differences in global site capabilities and diagnostic access can create major delays if not anticipated early.
Adaptive designs and mid-trial amendments are becoming more common, making operational flexibility essential. Regulators and payers also expect stronger evidence: not just response rates, but survival impact, quality-of-life improvements, and real-world value.
Dr. Keuker explains that with smaller patient populations and fast-moving diseases, the standards are higher. Trial goals must align with real-world expectations from the start.
A Strategic Priority for AML Developers
In today’s competitive landscape, AML sponsors must balance speed with scientific precision. Mutation-specific trial strategies require early integration of medical, operational, and regulatory expertise. As targeted therapies reshape AML development, only trials built with this mindset will be able to keep pace.
