NCT04160494

D2C7-IT With Atezolizumab for Recurrent Gliomas

A Phase 1 Trial of D2C7-IT in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Darell Bigner · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 1 study of atezolizumab in combination with D2C7-IT, a dual-specific monoclonal antibody (mAB) with a high affinity for both EGFRwt- and EGFRvIII-expressing cells, in patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Detailed description

Approximately eighteen patients with recurrent WHO grade IV malignant glioma will receive atezolizumab and D2C7-IT to determine the impact of the combination of D2C7-IT and atezolizumab on safety. D2C7-IT will be delivered intratumorally by Convection Enhanced Delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. The dose of D2C7-IT was reduced from 6920 ng/mL to 4613.2 ng/mL after the first 4 patients as a precaution due to safety events experienced by these 4 patients. Atezolizumab will be administered according to the FDA-approved dosing schedule of 1200 mg intravenously every 3 weeks, beginning \~2 weeks after the D2C7-IT infusion. Toxicity will be carefully monitored for each patient while they are on study for at least a year after D2C7-IT treatment or for at least 30 days after the final dose of atezolizumab if the patient continues atezolizumab on-study for longer than a year post-D2C7-IT. Of particular interest will be the incidence of adverse events that occur during the first 28 days after D2C7-IT treatment and the inflammatory events that occur during the first year after D2C7-IT treatment. The most common risks associated with D2C7-IT are effects related to tumor necrosis, neurologic changes (including changes in function, new or increased seizures, swelling of the brain, and injury to blood vessels), effects related to catheter placement or removal, and effects related to fluid infusion into the brain. The most common risks associated with atezolizumab are fatigue, decreased appetite, diarrhea, and nausea. Because atezolizumab works with the immune system, it can cause the immune system to attack normal organs or tissue and affect how they work.

Conditions

• Malignant Glioma

Interventions

Type	Name	Description
DRUG	D2C7-IT (6920 ng/mL via convection-enhanced delivery)	dual-specific mAB
DRUG	Atezolizumab (1200 mg every three weeks)	programmed cell death ligand 1 (PD-L1) blocking antibody
DRUG	D2C7-IT (4613.2 ng/mL via convection-enhanced delivery)	dual-specific mAB

Timeline

• Start date: 2020-02-25
• Primary completion: 2024-06-28
• Completion: 2027-12-01
• First posted: 2019-11-13
• Last updated: 2025-05-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study