NCT03576612

GMCI, Nivolumab, and Radiation Therapy in Treating Patients With Newly Diagnosed High-Grade Gliomas

Phase I Study of Neoadjuvant GMCI Plus Immune Checkpoint Inhibitor Combined With Standard of Care for Newly Diagnosed High-Grade Gliomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Candel Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this phase I trial is to test the safety of combining GMCI, an immunostimulator, plus nivolumab, an immune checkpoint inhibitor (ICI), with standard of care radiation therapy, and temozolomide in treating patients with newly diagnosed high-grade gliomas. Gene Mediated Cytotoxic Immunotherapy (GMCI) involves the use of aglatimagene besadenovec (AdV-tk) injection into the tumor site and oral valacyclovir to kill tumor cells and stimulate the immune system. Nivolumab is an immune checkpoint inhibitor that may also stimulate the immune system by blocking the PD-1 immune suppressive pathway. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors and temozolomide is a chemotherapy drug that kills tumor cells. Giving GMCI, nivolumab, radiation therapy, and temozolomide may work better in treating patients with high-grade gliomas

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety/maximum tolerated dose (MTD) of the combination of aglatimagene besadenovec (AdV-tk) given intra-cranially at the time of initial tumor resection followed by valacyclovir (GMCI), nivolumab, and standard of care (radiation therapy \[RT\]+temozolomide \[TMZ\]) in patients with high-grade gliomas (HGG). PRIMARY OBJECTIVES: I. To assess the safety/maximum tolerated dose (MTD) of the combination of aglatimagene besadenovec (AdV-tk) given intra-cranially at the time of initial tumor resection followed by valacyclovir (GMCI), nivolumab, and standard of care (radiation therapy \[RT\]+temozolomide \[TMZ\]) in patients with high-grade gliomas (HGG). SECONDARY OBJECTIVES: I. To evaluate safety and toxicity of this combined treatment regimen. II. To estimate overall survival. III. To estimate progression free survival. IV. Immune biomarkers, including serum extracellular vesicles (EVs). OUTLINE: Patients undergo tumor resection and receive AdV-tk injection into the wall of the resection cavity. Patients then receive valacyclovir orally three times per day for 14 days. Beginning on approximately day 8, patients undergo radiation therapy five days per week for 6 weeks. Temozolomide will be initiated on approximately day 15 after valacyclovir is completed and will continue until MGMT methylation status is known. If unmethylated, temozolomide will be discontinued: these patients will constitute Cohort 1. In Cohort 2 - patients with methylated MGMT - temozolomide will continue. If methylation status is unable to be determined, those patients will also continue receiving temozolomide (Cohort 2). Both cohorts will receive nivolumab intravenously every two weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 2 years, and then every 6 months thereafter.

Conditions

• Glioma, Malignant

Interventions

Type	Name	Description
BIOLOGICAL	AdV-tk	Given IT
DRUG	Valacyclovir	Given PO days 1-14; 1-3 days post surgery
RADIATION	Radiation	Undergo RT, 60Gy in 30 daily fractions M-F for 6weeks
DRUG	Temozolomide	Given PO during RT 75mg/m2 daily during RT Post RT cycle 1: 150mg/m2 days 1-5 150mg/m2 cycle 2-6: days 1-5 (150-200mg/m2)
BIOLOGICAL	Nivolumab	day 15 post surgery 240mg IV q2wks x 26 doses , up to 52 weeks
OTHER	Laboratory Biomarker Analysis	correlative studies

Timeline

• Start date: 2018-02-27
• Primary completion: 2023-06-30
• Completion: 2023-06-30
• First posted: 2018-07-03
• Last updated: 2025-02-14

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study