A Phase 1 Study of SRN-101 Administered Prior to Surgical Resection in Adults With Recurrent High-Grade Glioma.

A Phase 1 Window-of-Opportunity Study of SRN-101 Administered Prior to Surgical Resection in Adults With Recurrent High-Grade Glioma.

SRN-101 is designed to destroys tumor cells while simultaneously activating the immune system to fight cancer. This is a first in human, single arm study to evaluate SRN-101 for the treatment of adults with recurrent high-grade glioma (rHGG) who are eligible for resection.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioma; Brain Neoplasm; Recurrent High-Grade Gliomas
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging (MRI); Drug: SRN-101; Procedure: Blood Specimen Collection; Procedure: Surgical Resection

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of intratumoral administration of SRN-101 in participants with recurrent high-grade glioma (rHGG) undergoing resection.

II. To evaluate the biologic activity of SRN-101.

EXPOLORATORY OBJECTIVES:

I. To assess immunologic response to SRN-101. II. To identify potential pharmacodynamics biomarkers for SRN-101 activity.

OUTLINE: Participants will receive a single administration of SRN-101 during real-time magnetic resonance imaging (MRI)-guided convection-enhanced delivery (CED), followed by non-investigational surgical resection 7 to 21 days after SRN-101 administration. Participants will be followed for up to 5 years after surgical resection.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Neuro-Oncology New Patient Coordinator; Phone Number: 415-353-2193; Email: neurooncnewpatientcoord@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
      • Contact: Neuro-Oncology New Patient Coordinator; Phone Number: 415-353-2193; Email: neurooncnewpatientcoord@ucsf.edu
      • Principal Investigator: Nicholas Butowski, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥ 18 years of age.
2. Participants have received at least one prior line of standard-of-care treatment for high-grade glioma (HGG). Specifically, participants have received prior surgery that resulted in histopathologic diagnosis followed by treatment with radiation alone and/or radiation plus temozolomide.
3. Participants with recurrent high-grade glioma (rHGG) for whom resection is planned, and with a lesion that is accessible to convection-enhanced delivery (CED) therapy. Eligible tumor types include central nervous system (CNS) World Health Organization (WHO) Grade 4 astrocytoma isocitrate dehydrogenase (IDH) wild-type (WT) (i.e., glioblastoma), WHO Grade 4 astrocytoma IDH mutated, WHO Grade 3 astrocytoma IDH WT or mutated, and WHO Grade 3 oligodendroglioma IDH mutated, 1p19q codeleted. Participants may have had multiple recurrences.
4. Tumors must be supratentorial in location, and participants can only have a single lesion that is ≥ 1 centimeter and ≤ 4 centimeters in diameter.
5. Performance Level using the Karnofsky score ≥ 70%. Note: Neurologic deficits in participants with CNS tumors must have been stable for at least 7 days with no new deficits prior to study enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the Karnofsky performance score.
6. Predictable life expectancy of at least 3 months.
7. Participants must have adequately recovered from the acute toxic effects of all prior anti-cancer chemotherapy and must be at least 3 weeks from previous cytotoxic chemotherapy, 4 weeks from prior radiation therapy, and at least 2 weeks from any major surgery, with evidence of adequate wound healing.

8. Participants must have adequate organ function based on laboratory assessments obtained within 21 days prior to study treatment. Laboratory values obtained as part of standard of care within this timeframe may be used to satisfy eligibility criteria.

   Adequate bone marrow function:

   absolute neutrophil count ≥1,500/microliter (mcL) platelets ≥100,000/mcL

   Adequate hepatic function:

   total bilirubin ≤ 2x upper limit of normal (ULN) for their age Aspartate aminotransferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) ≤2 X institutional upper limit of normal alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤2 X institutional upper limit of normal Serum albumin ≥ 2 g/dL

   Adequate renal function:

   creatinine ≤ 1.5 x within institutional upper limit of normal OR creatinine clearance radioisotope (GFR) ≥ 70 mL/min/1.73 m2, calculated using the Cockcroft-Gault equation, unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2

   Adequate coagulation:

   Prothrombin time and international normalized ratio ≤ 1.5x ULN

   Note: Participants receiving anticoagulant therapy must be able to safely discontinue anticoagulation per institutional guidelines and the treating neurosurgeon's discretion prior to infusion of SRN-101.

9. Participants with seizure disorders may be enrolled if on a stable anticonvulsant dose and not experiencing refractory seizures in the last 3 months.
10. Agree to participate in the long-term safety follow-up.
11. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Disseminated disease or multifocal disease.
2. Pregnant or breastfeeding. Participants of childbearing potential and male participants with female partners of childbearing potential must agree to always use highly effective forms of contraception during the course of the study and for at least 3 months after completion of study intervention. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Participants of childbearing potential must have a negative blood pregnancy test within 21 days of commencement of study intervention. Participants must refrain from donating sperm during the course of the study and for at least 3 months after completion of study intervention.
3. History of active liver disease, including Hepatitis B or Hepatitis C or human immunodeficiency virus (HIV).
4. Another concurrent tumor immunotherapy.
5. Initiation and/or escalation of systemic immunosuppressive therapy (including corticosteroids) within 7 days prior to study initiation, except protocol-required peri-procedural dexamethasone. Participants already on dexamethasone (at a maximum dose of 4 mg per day) are eligible.
6. Known or suspected hypersensitivity to Gadoteridol, its excipients, or other gadolinium-based contrast agents.
7. Recent onset of neurologic dysfunction or abnormality that is deemed by the Investigator to prevent patient participation.
8. Inability, or potential inability, to comply with the safety monitoring requirements of the study, as determined by the Investigator's opinion.
9. Other comorbidities that the Investigator believes will negatively impact the participant's ability to benefit from or tolerate this study.
10. Inability to undergo an MRI.
11. Radiographic evidence that the target lesion or an associated treatment or resection cavity directly communicates with the ventricular system, or determination by the treating neurosurgeon that adequate CED of the target lesion cannot be performed without clinically meaningful leakage of infusate into a cerebral spinal fluid (CSF) space.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SRN-101 Run-in Dose Level - 1.6E12 vg (First Participant); Participants will receive a single intratumoral administration of SRN-101 at a dose of 1.6E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.	Procedure: Magnetic Resonance Imaging (MRI); Undergo imaging; Drug: SRN-101; Given Intratumoral; Procedure: Blood Specimen Collection; Perform blood work; Procedure: Surgical Resection; Undergo surgery; Other Names: Undergo surgical resection tumor tissue
Experimental: SRN-101 Dose Level - 5.0E12 vg (Subsequent Participants); Participants will receive a single intratumoral administration of SRN-101 at a dose of 5.0E12 vector genomes (vg) via real-time MRI-guided convection-enhanced delivery (CED). Following administration, participants will be monitored for safety and tolerability through the day of tumor resection, which will take place 7 to 21 days after SRN-101 administration.	Procedure: Magnetic Resonance Imaging (MRI); Undergo imaging; Drug: SRN-101; Given Intratumoral; Procedure: Blood Specimen Collection; Perform blood work; Procedure: Surgical Resection; Undergo surgery; Other Names: Undergo surgical resection tumor tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants reporting treatment-emergent adverse events	Treatment-emergent adverse events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	Up to 21 days
Proportion of participants reporting adverse events of special interest	Adverse events of special interest (AESI) will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0	Up to 21 days
Quantification of SRN-101 vector copy number	SRN-101 vector copy number will be measured in resected tumor tissue, peripheral blood, and cerebrospinal fluid (if available) using quantitative polymerase chain reaction (qPCR). Results will be summarized descriptively.	Up to 21 days
Quantification of hIFNβ transcript and protein levels	hIFNβ transcript and protein levels will be measured in resected tumor tissue, peripheral blood, and cerebrospinal fluid (CSF; if available) using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results will be summarized descriptively.	Up to 21 days

Collaborators and Investigators

• Sponsor: Nicholas Butowski
• Collaborators: Siren Biotechnology
• Investigators: Principal Investigator: Nicholas Butowski, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: September 10, 2026
• First Submitted That Met QC Criteria: September 10, 2026
• First Posted (Actual): September 18, 2026

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Glioma; Brain Neoplasms; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy; Blood Specimen Collection
• Other Study ID Numbers: 26104; NCI-2026-06804 (Registry Identifier: NCI Clinical Trials Reporting System (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No