Novel Sonodynamic Therapy Doubles Survival in Recurrent Glioblastoma

Tumor in brain : © peterschreiber.media - stock.adobe.com

Sonodynamic therapy (SDT) was shown to more than double median overall survival (OS) and triple progression-free survival (PFS) compared with historical outcomes in patients with recurrent or refractory high-grade gliomas, according to findings from a first-in-human, phase 1/2 clinical trial (NCT05362409).¹

The data were presented by Michael Schulder, MD, at the 2024 Society of Neuro-Oncology (SNO) Annual Meeting, showing a median OS of 15.7 months, which is a significant improvement over the historical benchmark of 6 to 8 months for patients with recurrent glioblastoma. The median PFS also improved to 5.5 months vs the standard 1.8 months.

For safety, the therapy exhibited a robust safety profile with no treatment-related deaths, serious adverse events, or significant toxicities reported.

"Glioblastomas are the most common and aggressive primary brain cancer, presenting a devastating diagnosis for patients and their families," said David Reardon, MD, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, and member of the Alpheus Medical Scientific Advisory Board. "Current treatment options are limited and often ineffective due to the diffuse spread of the disease across the blood-brain barrier and often across the entire hemisphere, making it universally fatal with a rapid timeline.”

“The early clinical results of Alpheus's therapy are promising, offering hope for this new approach. I look forward to further exploring the potential benefits of their SDT therapy for this patient population who are in critical need of an effective solution," continued Reardon.

This non-invasive approach combines low-intensity diffuse ultrasound with oral 5-aminolevulinic acid. The treatment works by selectively destroying cancer cells across the entire hemisphere while sparing healthy tissue. Additionally, SDT is delivered in an outpatient setting and eliminates the need for imaging or sedation, which makes it more accessible than traditional therapies.

The open-label, phase 1/2 trial enrolled 12 patients across 3 escalating treatment durations of 60, 90, and 120 minutes per monthly session. The study aims to assess safety, determine the optimal treatment duration, and evaluate preliminary efficacy.

Enrollment is open to patients aged 18 years and older with a WHO performance status of ≤ 2 at screening, unifocal or multifocal tumor confined to the supratentorial compartment, adequate bone marrow and organ function, and adequate coagulation function.² Any toxicity from prior anti-cancer therapy must be resolved to the patient's baseline level or ≤ grade 1, excluding alopecia.

The study is divided into 3 parts. For part A, patients must have a histopathologically confirmed diagnosis of high-grade glioma (HGG) with radiographic evidence of recurrence following prior therapy that included radiotherapy. Eligible histologies, based on the 2021 WHO classification, include astrocytoma (WHO grades 3 and 4, including subtypes) and oligodendroglioma (WHO grade 3, including subtypes). For parts B and C, eligibility is restricted to patients with a histopathologically confirmed diagnosis of glioblastoma, with radiographic evidence of recurrence after prior radiotherapy. Additionally, while part A allows patients with any type of HGG and any number of recurrences, parts B and C are limited to patients experiencing their first recurrence of glioblastoma.

The company now plans to launch a randomized, controlled trial at multiple centers in the US in 2025 to further validate the efficacy and safety of SDT, potentially paving the way for regulatory approval.¹

"In addition to the strong safety data and early indications of efficacy, Alpheus' non-invasive SDT therapy stands out for its ease of use - a significant improvement over the uncomfortable and often toxic treatments currently available for this rapidly fatal condition," stated Schulder, Director of the Brain Tumor Center at Northwell Health, and one of the trial's primary investigators, during the SNO presentation. "We look forward to expanding the ability for patients to receive this promising therapy."

REFERENCES:

1. Alpheus Medical announces positive phase 1/2 trial results for the treatment of recurrent high-grade gliomas. News release. Alpheus Medical, Inc. November 24, 2024. Accessed December 3, 2024. https://tinyurl.com/yds2bj9v

2. Study to evaluate 5-ALA combined with CV01 delivery of ultrasound in recurrent high grade glioma. ClinicalTrials.gov. Updated February 22, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT05362409