“DIPG is the deadliest cancer known to man. We cannot send kids home with one oral drug and expect that to help. Using a combination of drugs is crucial in order to make significant progress in the treatment of DIPG.”
— Dr. Matt Dun, biomedical scientist and
DIPG Dad to Josie, who passed away in 2019
For the third year in a row, the ChadTough Defeat DIPG Foundation announced its support for a first-of-its-kind trial platform called Diffuse Midline Glioma – Adaptive Combinatorial Therapy (DMG-ACT), bringing the total dollars committed to more than $1.5 million. This promising project is a collaboration between the world’s leading brain cancer experts, encompassing 30 research groups from 7 countries around the world.
Over the last six decades, little was known about DMG/DIPG tumors, which claim the lives of more than 1,000 children each year worldwide. Radiation had traditionally been the only standard of care, and clinical trials that tested just one singular drug saw little improvement in patient outcomes.
Things began to change in recent years when grieving parents, determined to make a difference, began donating their child’s postmortem tumor tissue to science. Biopsy procedures had become much safer and allowed for more upfront tissue sampling as well. With the ability to investigate these tumor specimens, scientists were able to gain a new understanding of the biology of these tumors, and doctors are now convinced the disease will not be cured by a single drug alone.
Given the genetic diversity of these complicated tumors, researchers like Dr. Sabine Mueller and Dr. Javad Navarian, both of the DMG/DIPG Center in Zurich, believe a personalized therapy approach is crucial in uncovering effective treatment options.
In October of 2021, they launched the DMG-ACT by forming a collaboration among the world’s leading brain cancer experts and established a biology-informed, adaptive, and progressive trial, designed to deliver more rapid progress for children suffering from DIPG/DMG by testing a combination of two or more drugs. By the end of 2022, 52 patients had been enrolled in the DMG-ACT. The trial had investigated more than 100 drugs in the lab and a combination of two drugs, ONC201 and Paxalisib, in patients. A combination of 5 different drugs is now being vetted for addition to the trial.
“So far, we have shown this trial platform is safe and feasible in 22 sites in the U.S., Europe, and Australia,” explained Dr. Carl Koschmann of Michigan Medicine, who serves as Co-Principal Investigator for the trial. “In 2023, we will get our first early assessments of efficacy and begin studying the diverse array of correlated samples.”
Through this unprecedented trial platform setup, scientists across the world are able to share their latest preclinical data, allowing for more rapid progress in the care of patients. This constant feedback loop is an innovative aspect, setting it apart from most prior experimental therapies for children facing DMG/DIPG. Support from private funders, like the ChadTough Defeat DIPG Foundation, is imperative in the success of trials such as the DMG-ACT. This allows researchers, in
the early stages of their investigation, to gather the data necessary to qualify for larger government grants. The grants provided by ChadTough for preliminary research through DMG-ACT helped lead to an additional $6.4 million in federal grants, thus
magnifying the impact of the dollars we are investing in this critical work.
“Simply put,” said Dr. Koschmann, “the DMG-ACT would not have been possible without the support of the ChadTough Defeat DIPG Foundation. For those of us involved, we feel this will finally provide the jumps in improved survival for DMG that was seen in leukemia 40 to 50 years ago.”