Evaluating a CNS-Penetrant EGFR Inhibitor in Brain Cancer

Shwetal Mehta, PhD, spoke with CancerNetwork^® about ongoing research efforts that her institution is organizing in the development of novel treatments for patients with brain cancer.

According to Mehta, the deputy director and pre-clinical core leader at the Ivy Brain Tumor Center of Barrow Neurological Institute in Phoenix, Arizona, she and her colleagues are assessing treatment with an investigational fourth-generation EGFR inhibitor that has demonstrated brain-penetrant qualities. As part of identifying potential resistance mechanisms associated with this agent, she described a liquid biopsy program in which investigators sample cerebrospinal fluid from patients who are currently undergoing treatment to determine the extent of therapeutic activity and symptom progression.

In November 2023, investigators announced that the first patient had received treatment as part of a phase 0/1 trial (NCT06072586) assessing the brain-penetrant MasterKey inhibitor BDTX-1535 among those with recurrent high-grade glioma harboring oncogenic EGFR mutations. The trial’s primary objective is determining how much the agent accumulates in the tumor tissue of patients; those who demonstrate adequate drug penetration may be eligible to continue treatment as part of an expansion phase.

Transcript:

There are several other novel clinical trials that we are part of. One of them is with an EGFR inhibitor. In neuro-oncology, people have been trying to target EGFR, which has been quite commonly mutated in [glioblastoma], for a while. It’s not a new target. Normally, people don’t want to get into the space, but this drug that we are testing is a fourth-generation EGFR inhibitor. It’s brain-penetrant. In the past, people have tested drugs that were not brain-penetrant. We’re really excited to ask more questions.

We know the drug gets in, [but] are there specific patient populations that are going to benefit from this drug? Is that what we need to identify? Are there going to be resistance mechanisms that we need to figure out and address? We have a whole new program of liquid biopsy where we sample cerebrospinal fluid from patients while they’re on treatment to see if the tumor is evolving [or] changing. If that can immediately give us an answer even before we start seeing symptoms of progression, [we might see] if there is a way to pivot, add a new therapy, and help these patients.

Reference

Ivy Center announces first patient treated in targeted phase 0/1 clinical trial for high-grade glioma study tests targeted agent, BDTX-1535, an EGFR inhibitor with brain-penetrant properties. News release. Ivy Brain Tumor Center. November 6, 2023. Accessed January 13, 2025. https://tinyurl.com/mw8dcxzk