NCT04201873

Pembrolizumab and a Vaccine (ATL-DC) for the Treatment of Surgically Accessible Recurrent Glioblastoma

Phase I Surgical Trial to Evaluate Early Immunologic Pharmacodynamic Parameters for the PD-1 Antibody Pembrolizumab With Autologous Tumor Lysate-Pulsed Dendritic Cell Vaccination in Patients With Surgically Accessible Recurrent/Progressive Glioblastoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and how well of pembrolizumab and a vaccine therapy (ATL-DC vaccine) work in treating patients with glioblastoma that has come back (recurrent) and can be removed by surgery (surgically accessible). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vaccines, such as ATL-DC vaccine, may help the body build an effective immune response to kill tumor cells. Giving pembrolizumab and ATL-DC vaccine may work better in treating patients with glioblastoma compared to ATL-DC alone.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the influence of pembrolizumab on the cell cycle-related genetic signature within the tumor microenvironment of progressive/recurrent glioblastoma. II. To evaluate the influence of adjuvant autologous tumor lysatepulsed dendritic cell (ATL-DC) vaccination on peripheral T cell responses. III. To evaluate the safety and tolerability of pembrolizumab and ATL-DC vaccination in progressive/recurrent glioblastoma. SECONDARY OBJECTIVES: I. To estimate the 6 month progression-free survival (PFS6) based on Response Assessment in Neuro-Oncology (RANO) criteria in patients treated on both arms of the clinical trial. II. To calculate the overall survival of recurrent glioblastoma patients treated on both arms of the clinical trial. EXPLORATORY OBJECTIVES: I. To evaluate the associations between exploratory biomarkers, clinical outcomes, and adverse events which include: Ia. Estimating the correlation of quantitative assessments of tumor infiltrating lymphocyte (TIL) density or the interferon (IFN) gamma-associated genetic signature with clinical responses to pembrolizumab and ATL-DC in recurrent glioblastoma patients. Ib. Estimating the efficacy of pembrolizumab and ATL-DC through PFS6, PFS and overall survival (OS) as defined by RANO. Ic. Estimating the efficacy of pembrolizumab and ATL-DC through PFS6, PFS, and OS as defined by immunotherapy RANO (iRANO). Id. Exploring whether oligoclonal T cell populations within tumor tissue are similarly expanded in peripheral blood after ATL-DC vaccination and/or pembrolizumab, and correlating with clinical responses. Ie. Exploring whether changes in specific magnetic resonance imaging (MRI) parameters correlate with tumor and peripheral blood immune responses. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP A: Beginning 14 days prior to scheduled surgery, patients receive pembrolizumab intravenously (IV) over 30 minutes. After surgery, patients receive pembrolizumab IV over 30 minutes on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC intradermally (ID) with poly ICLC intramuscularly (IM) every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. GROUP B: Beginning 14 days prior to scheduled surgery, patients receive placebo IV. After surgery, patients receive placebo IV on day 1. Cycle repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive ATL-DC ID with poly ICLC IM every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Conditions

• Recurrent Glioblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Dendritic Cell Tumor Cell Lysate Vaccine	Given ID
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Placebo Administration	Given IV
DRUG	Poly ICLC	Given IM

Timeline

• Start date: 2020-01-08
• Primary completion: 2026-08-01
• Completion: 2027-08-01
• First posted: 2019-12-17
• Last updated: 2025-08-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study