The Ivy Brain Tumor Center at Barrow Neurological Institute is accelerating the development of novel therapies for brain cancer, focusing on early-phase clinical trials designed to efficiently identify and advance promising drug candidates. The center employs a pharmacokinetic- and pharmacodynamic-driven strategy to optimize resource allocation and expedite the evaluation of therapeutic agents with potential activity in the brain.
Early Phase Trial Program
Shwetal Mehta, PhD, deputy director and pre-clinical core leader at the Ivy Brain Tumor Center, highlighted the institution's commitment to moving drugs through the development pipeline. The goal is to identify drugs with activity in the brain, advance those candidates, and eliminate ineffective treatments, thereby conserving resources and patient time. Mehta noted, "Our goal was to move drugs through this pipeline using pharmacokinetics- and pharmacodynamics-based approaches to identify drugs that have activity in the brain, move those good drugs forward, and then also weed out the ones that are not good."
Expansion to Phase 3 Studies and Novel Drug Classes
Having established a robust early-phase program, the Ivy Brain Tumor Center is now expanding its focus to include Phase 3 studies. The center is particularly interested in exploring new classes of agents, such as proteolysis targeting chimeras (PROTACs) and antibody-drug conjugates (ADCs), which have demonstrated efficacy in other tumor types. Mehta explained, "We’ve seen that we were capable of not just doing these early phase clinical trials [but entering] this phase of moving drugs into phase 3 [studies]. That’s exciting."
Clinical Trial Evaluating BDTX-1535
As part of its early-phase trial program, the center is conducting a Phase 0/1 clinical trial (NCT06072586) evaluating BDTX-1535, a brain-penetrant fourth-generation EGFR inhibitor, in patients with recurrent high-grade glioma harboring oncogenic EGFR alterations or fusions. The trial incorporates liquid biopsy, using cerebrospinal fluid samples to monitor potential tumor evolution during treatment.
Biomarker Testing and Targeted Therapies
The Ivy Brain Tumor Center emphasizes the importance of biomarker testing, including gene sequencing and immunohistochemistry, to identify targetable alterations in brain cancer patients. Mehta cited vorasidenib (Voranigo), an FDA-approved targeted therapy for patients with actionable IDH mutations, as an example of how biomarker testing can guide treatment decisions. This approach aligns with the center's patient-driven philosophy, ensuring that patients receive timely and personalized treatment strategies.
