PHOENIX—The Ivy Brain Tumor Center at the Barrow Neurological Institute and Houston-based Salarius Pharmaceuticals Inc. have launched a collaborative partnership to test Salarius’ therapeutic candidate, seclidemstat, for the treatment of glioblastoma. Glioblastoma affects 1.4 million patients worldwide and 138,000 in the United States, and by the end of this year, it’s estimated another 256,000 people will be diagnosed with glioblastoma.
Despite years of coordinated efforts by the scientific community, new experimental drugs continue to be ineffective against what is commonly considered the most difficult type of cancer to cure. From 1998 to 2014, at least 78 new brain tumor drugs were developed and tested in patients, but only three gained FDA approval.
For this reason, Barrow and Salarius will take a more direct approach by launching the most comprehensive preclinical study to date, evaluating the effect of targeting LSD1 (lysine-specific histone demethylase 1A), a key enzyme that has increased expression in tumors of brain cancer patients.
Seclidemstat is a reversible LSD1 inhibitor that works by inhibiting LSD1’s enzymatic and protein-scaffolding functions. It is currently being tested by Salarius in a Phase 1 study for refractory or relapsed Ewing’s sarcoma, and a Phase 1 study for advanced solid tumors. Seclidemstat is among the most clinically advanced reversible LSD1 inhibitors in development, and its potential effect on glioblastoma represents a promising new therapeutic treatment option.
“Seclidemstat is highly differentiated LSD1 inhibitor with unique properties that may enable efficacy in a broader range of cancer types,” said Dr. Nader Sanai, director of the Barrow Brain Tumor Research Center. “Seclidemstat and/or its analogs have shown the potential for synergies with chemotherapies and other targeted agents. This gives us hope that seclidemstat may be effective in treating a number of aggressive cancers, including glioblastoma.
“Our shared goal with Salarius is to address the lag in new drug development for malignant brain tumors by accelerating early-phase clinical trials for first-in-class agents like seclidemstat,” Sanai adds.
The Ivy Brain Tumor Center’s advanced preclinical capabilities include patient-derived xenograft animal models and state-of-the-art pharmacokinetics and pharmacodynamics core facilities, according to its website. A key component is leveraging the Ivy center’s core capabilities in collaboration with Salarius to perform in-house survival studies, advanced animal imaging, toxicology assessment, and in-vivo pharmaco-metabolic analyses.
Should the preclinical phase provide sufficient evidence for positive drug effects, the program will move to the subsequent clinical evaluation of seclidemstat, Sanai reports. This will take place within the context of a Phase 0 clinical trial.
David Arthur, president and CEO of Salarius Pharmaceuticals, commented, “Salarius is well positioned and highly motivated to provide a new therapeutic option for a number of cancers with high unmet medical need. We are inspired by the Ivy Brain Tumor Center’s unwavering commitment to pursuing advances in glioblastoma treatment and look forward to this creative and vital research partnership.”
For most brain tumor patients, enrolling in conventional clinical trials involves a leap of faith, according to Sanai, who is a neurosurgical oncologist specializing in treating tumors of the brain and spine.
“After being prescribed a new agent, you struggle through significant side effects and the agonizing wait for brain imaging several months later,” Sanai says. “Under ideal circumstances, the experimental therapies arrests disease progression and, in these cases, the time and effort invested by you and your family were worthwhile. Unfortunately, a more common result is that the new therapy is ineffective, costing you precious time and energy as you, once again, face another set of imperfect treatment options.”
“Our clinical trials are precision medicine studies, which means that each patient’s tumor is first defined by its distinct signature of genetic abnormalities and each experimental treatment regimen is then selected to attack that specific code,” he adds, noting that “All of our studies integrate a ‘Phase 0’ clinical trial design, which enables us to test dozens of new therapies quickly in brain tumor patients—not just in the laboratory—and get patients the new regimen that fits their exact circumstances.”
The Ivy Brain Tumor Center is home to the largest Phase 0 clinical trials program for brain tumor patients in the world. Patients with specific genetic signatures receive a single dose of a matched experimental regimen a day prior to brain tumor operation. During surgery, tissue samples are collected and then tested in the lab, which means that shortly after surgery, the Phase 0 team can identify which therapies penetrated and impacted a patient’s tumor. Once the experimental regimen is confirmed to affect a patient’s tumor, the patient is ‘graduated’ to maximum therapeutic doses of that regimen.
Phase 0 patients who graduate to therapeutic dosing will know their tailored treatment regimen is based upon direct evidence of their individual tumor’s responsiveness, Sanai remarks. Conversely, Phase 0 studies also identify which specific strategies will not work for individual patients and tumors.
Phase 0 studies are “not synonymous with first-in-human studies,” the Ivy Brain Tumor Center points out. “While some of our experimental agents are being tested in patients for the first time ever, many more of our clinical trials consist of new agents and new combinations of agents that are proven safe in patients, but have never been trialed as a therapy for brain tumors.”