A Study of SRN-101 Gene Therapy in Adults With Recurrent High-Grade Glioma (ALERT-1)

ALERT-1 is a Phase 1/2 study evaluating the safety and preliminary anti-tumor activity of SRN-101, an investigational gene therapy, in adults with recurrent high-grade glioma. High-grade glioma is a type of brain cancer. This study is for adults whose cancer has returned for the first time and for whom surgical removal of the tumor is not planned. SRN-101 uses an adeno-associated virus (AAV) to deliver a gene for human interferon beta, a protein within the tumor. The safety and effectiveness of SRN-101 in this setting have not been established. Each participant will receive one infusion of SRN-101 directly into the brain tumor during an MRI-guided procedure. The study will first evaluate different dose levels and then evaluate a selected dose in additional participants. Participants will have MRI scans, blood tests and other health assessments, and follow-up visits to assess safety and changes in their cancer.

Inclusion Criteria: * First recurrence of high-grade glioma for which surgical resection is not planned * Eligible tumor type, including Grade 3 or Grade 4 astrocytoma, Grade 3 oligodendroglioma, glioblastoma, or diffuse hemispheric glioma, with histologic confirmation of malignancy * Received prior standard treatment for high-grade glioma, including surgery followed by radiation alone or radiation with temozolomide * A single tumor located above the tentorium that is accessible for treatment with SRN-101 and is 1 to 4 centimeters in diameter * Karnofsky performance status of at least 70% * Life expectancy of at least 3 months * Recovered from the acute effects of prior anti-cancer treatment and meets required waiting periods following prior chemotherapy, radiation therapy, and major surgery * Adequate bone marrow, kidney, liver, and blood-clotting function * Willing to participate in the long-term safety follow-up study Exclusion Criteria: * Disseminated or multifocal disease * Pregnant or breastfeeding * History of or current liver disease, including active hepatitis B or hepatitis C, or human immunodeficiency virus * Receiving another tumor immunotherapy * Recent initiation or increase in systemic immunosuppressive therapy, including corticosteroids, except as permitted by the protocol * Recent neurologic dysfunction or abnormality that, in the Investigator's judgment, would prevent participation * Unable to comply with the study's safety monitoring requirements * Other medical conditions that, in the Investigator's judgment, could negatively affect the participant's ability to benefit from or tolerate the study * Unable to undergo magnetic resonance imaging (MRI)