NCT03707457

Biomarker-Driven Therapy Using Immune Activators With Nivolumab in Patients With First Recurrence of Glioblastoma

Phase I Protocol to Assess Safety of Biomarker-Driven Therapy Using Selective Immune Activators in Combination With Anti-PD-1 (Nivolumab) in Patients With First Recurrence of Glioblastoma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research is being done to test if it is safe to give nivolumab with targeted immunotherapy drugs for recurrent glioblastoma (GBM), a type of brain tumor. The study doctors believe that giving immunotherapy drugs that match the biomarkers in a tumor will help the immune system fight the tumor. Tumor tissue collected during surgery will be tested for certain biomarkers to determine which immunotherapy might best target the tumor. The combination immunotherapy arms include: Arm A: Nivolumab + anti-GITR Arm B: Nivolumab + IDO1 inhibitor Arm C: Nivolumab + Ipilimumab

Detailed description

PRIMARY OBJECTIVE 1\. To determine safety of each of the following study agents, anti-GITR, IDO1 inhibitor, and ipilimumab, in combination with nivolumab (BMS-936558) flat dose in patients with first recurrence of GBM. SECONDARY OBJECTIVES 1. To estimate toxicity 2. To estimate progression-free survival 3. To estimate overall survival 4. To evaluate pain for patients undergoing the treatment of anti-GITR, IDO1 inhibitor, and ipilimumab, in combination with nivolumab. EXPLORATORY OBJECTIVES 1. To characterize the immune response during and after treatment as measured by immunohistochemistry, and other T cells etc. in peripheral blood 2. To characterize the pharmacodynamic and genomic activity in tumor tissue as target inhibition 3. To characterize radiographic response 4. Genetic characterization of correlative samples

Conditions

• Glioblastoma
• Glioblastoma Multiforme

Interventions

Type	Name	Description
DRUG	Nivolumab	Patients receive nivolumab intravenously (IV) over 30 minutes on Day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
DRUG	Anti-GITR Monoclonal Antibody MK-4166	Patients receive anti-GITR intravenously (IV) over 30 minutes on Day 1 of the first cycle of nivolumab after arm assignment. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
DRUG	IDO1 inhibitor INCB024360	Patients receive IDO1 inhibitor by mouth daily beginning on Day 1 of the first cycle of nivolumab after arm assignment. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
DRUG	Ipilimumab	Patients receive ipilimumab intravenously (IV) over 90 minutes on Day 1 of the first cycle of nivolumab after arm assignment. Courses repeat every 21 days for up to 4 doses in the absence of disease progression or unacceptable toxicity.

Timeline

• Start date: 2019-03-22
• Primary completion: 2019-11-30
• Completion: 2020-06-18
• First posted: 2018-10-16
• Last updated: 2020-07-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study