Five Leading Cancer Centers Unite to Target CD123 and Eradicate Hidden Leukemia Cells

A multi-site trial pairs targeted therapy with next-generation MRD testing to track residual disease and uncover vulnerabilities in leukemia cells

CAMBRIDGE, Mass., Dec. 11, 2025 /PRNewswire/ -- Acute myeloid leukemia (AML) is an aggressive blood cancer, with overall survival remaining approximately 30% at five years despite advances in therapy. Even when patients achieve remission, the disease often returns, fueled by a small number of leukemia cells that survive initial treatment, known as measurable residual disease (MRD). These remaining cells are major drivers of relapse and are linked with poorer outcomes, yet no standard therapy exists to eliminate them. Addressing MRD has become one of the most urgent clinical challenges in AML, and the focus of the 'Eradicating Measurable Residual Disease in AML' Break Through Cancer TeamLab.

"MRD is like the bulk of an iceberg hidden beneath the surface. We can treat the disease we see, but the real challenge is determining how much remains unseen" said Jacqueline Garcia, assistant professor of medicine at Harvard Medical School and medical oncologist at Dana-Farber Cancer Institute and lead investigator on the trial. "We have billions of blood cells in our body, and the questions are: How much disease is truly left over? How do we measure it? And how do we quantify our patient's risk?"

Why Target CD123
CD123, a leukemia cell-surface marker present in more than 80% of cases, is involved in cancer cell growth and survival and is especially elevated in high-risk subtypes. "We wanted a study that could have broad reach across more subgroups of patients," said Garcia. "CD123 is present on the surface of AML cells and early leukemia stem cells which makes it a meaningful way to target residual disease."

This multi-site study will evaluate targeting CD123 in combination with two established AML therapies. Tagraxofusp (Stemline), a CD123-directed immunotoxin already FDA-approved for another blood cancer, "binds to cells expressing CD123, and delivers a diptheria toxin payload directly into the cell," Garcia explained. Work led by fellow TeamLab investigator Dr. Andrew Lane, co-leader of the Dana-Farber/Harvard Cancer Center Leukemia Program, showed that azacitidine and venetoclax can boost sensitivity and enhance anti-leukemic activity in this combination, forming the scientific rationale for combining all three therapies. "By adding two approved treatments for active AML, we're testing if this combination can safely eradicate leftover disease and convert patients from MRD positive to negative" Garcia noted. Early clinical signals reinforce this strategy. In a recent phase 1b study in patients with newly diagnosed AML, this combination achieved a 69% response rate, and among patients in remission, nearly 71% achieved MRD-negativity.

A Trial Designed to Learn as well as Treat
This phase 1/2 trial (NCT07148180) is now active at Dana-Farber Cancer Institute and will be jointly conducted across four of Break Through Cancer's clinical centers including Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Harnessing the deep expertise within the Eradicating Measurable Residual Disease in AML TeamLab across the four clinical sites and MIT's Koch Institute for Integrative Cancer Research, this study will generate an unusually rich scientific dataset. Blood and bone marrow samples collected throughout treatment will be analyzed using state-of-the-art approaches such as circulating tumor DNA profiling, single-cell sequencing and immunophenotyping, and advanced proteomic analyses. "Alongside routine clinical tests, we are also developing new ultrasensitive assays to detect low levels of residual disease and running research assays to learn why certain leukemia cells persist," added Garcia.

Together, these integrated analyses are designed to monitor how patients respond, reveal why MRD occurs, how it evolves, and which vulnerabilities may be exploited to improve future treatment strategies. By pairing deep biological discovery with clinical testing, the TeamLab aims to both eradicate MRD today and reshape how residual disease is detected and addressed in AML going forward.

"This study is part of Break Through Cancer's broader work addressing minimal residual disease," said Tyler Jacks, PhD, president of Break Through Cancer. "Eliminating every last cancer cell is a formidable challenge, but one we can meaningfully advance when apply to best of science and work together."

About Break Through Cancer
Founded in 2021, Break Through Cancer empowers outstanding researchers and physicians to both intercept and find cures for several of the deadliest cancers by stimulating radical collaboration among outstanding cancer research institutions, including its founding partners: Dana-Farber Cancer Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Memorial Sloan Kettering Cancer Center, MIT's Koch Institute for Integrative Cancer Research, and The University of Texas MD Anderson Cancer Center.

The Foundation is supported by a Board of Directors from the five partner institutions and a Scientific Advisory Board of U.S. cancer experts. The Foundation was launched with an extraordinary challenge pledge of $250 million from Mr. and Mrs. William H. Goodwin, Jr. and their family, and the estate of William Hunter Goodwin III.

For further information, please visit the Foundation's website at www.breakthroughcancer.org.

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Soracha Ward
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SOURCE Break Through Cancer