Project Summary:
Brain tumors are the most common solid tumor of childhood. However, for glioblastoma, medulloblastoma, and ependymoma the cure rate remains only 60-70%. Once pediatric brain tumors recur or progress, the disease is usually rapidly fatal. Repeated cycles of chemotherapy can lead to resistance. However, the immune response differs fundamentally from the response to chemotherapy in that repeated cycles of immunotherapy may actually increase the beneficial anti-tumor effects. A suitably activated immune system is capable of allowing otherwise ineffective chemotherapy to now become potent and effective.
David Munn, MD, from Augusta University, is conducting an open-label Phase 1b study to test if adding ibrutinib can restore systemic immune activation and functional anti-tumor activity in patients 12 to 25 years old with brain cancer who are highly resistant, actively progressing, and have already become resistant to chemoimmunotherapy with indoximod alone. The trial comprises a dose-finding cohort to establish safety and dosing of ibrutinib, then an expansion cohort to evaluate the efficacy of the combination.
Research Update April 2024:
Brain tumors that recur or are resistant to treatment represent the leading cause of cancer deaths in children. The outcome for these patients is dismal, and has changed little in 20 years. Thus, better therapies are urgently needed. Dr. Munn’s current clinical trial uses a new immunotherapy drug called indoximod, developed in their laboratory, that is combined with conventional chemotherapy, plus the approved drug ibrutinib, to offer an additional treament option for pediatric brain tumor patients.
In his Catapult-funded clinical trial, Dr. Munn and his team are trying to determine if adding the ibrutinib drug, which they recently showed works together with indoximod, will enhance and extend the therapeutic response in these desperately ill patients who do not benefit from indoximod alone. During the first 6 months of funding, Dr. Munn and his team have set up the fully functioning infrastructure for the phase 1 clinical trial, and enrolled 8 patients and counting.
An important scientific component of the trial is the collection of serial blood samples that they are able to obtain from each patient. The samples are analyzed for immune activation, and stored away in a frozen archive for detailed molecular analysis of immune response. The results of these laboratory studies are showing a large immune response in the responding patients, which supports their hypothesis that treating patients with ibrutinib plus indoximod and chemotherapy mav provide a new treatment option for children with brain tumor which were previously untreatable. This level of detailed molecular analysis has never been performed on a pediatric chemoimmuno- therapy trial before, thus the initial results are extremely exciting and also have a high potential to impact the entire field of pediatric oncology.
