Recurrent Glioblastoma, IDH-Wildtype Clinical Trial
Official title:
Phase 2 and Biomarker Trial of Anti-TIGIT and Anti-PDL1 in Patients With Recurrent Glioblastoma
This phase II trial compares the safety, side effects and effectiveness of atezolizumab with tiragolumab to atezolizumab alone in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Glioblastoma is the most common primary brain cancer in adults and despite aggressive treatment, it is nearly always fatal. Currently, there are limited effective treatment options in patients that have recurrence. Immunotherapy has been shown to be effective in other types of cancer and may be an appealing potential treatment option for recurrent glioblastoma. Immunotherapy with monoclonal antibodies, such as atezolizumab and tiragolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Study doctors also want to learn if a tumor infiltrating T lymphocyte (TIL) response is helpful to determine the benefit of the combination of study drugs compared to the usual approach. TILs are a type of immune cell that has moved from the blood into a tumor. TILs can recognize and kill tumor cells. Giving atezolizumab with tiragolumab may be safe, tolerable and/or effective compared to atezolizumab alone in treating patients with recurrent glioblastoma.
PRIMARY OBJECTIVE: I. To evaluate the impact of combination atezolizumab plus tiragolumab on progression free survival. SECONDARY OBJECTIVES: I. To evaluate the impact of atezolizumab, tiragolumab, or their combination on tumor infiltrating T lymphocyte (TIL) density in glioblastoma patients. II. To evaluate the safety of study drug therapy in patients with glioblastoma in the (neo)adjuvant setting. III. To estimate therapeutic benefit of atezolizumab and tiragolumab in the recurrent glioblastoma patient population. IV. To evaluate the impact of baseline tumor mutation burden and expression on response. EXPLORATORY OBJECTIVES: I. To evaluate the impact of combination treatment on the tumor immune microenvironment. II. To evaluate the impact of combination treatment on the peripheral immune microenvironment. III. To evaluate the peripheral and central pharmacokinetics of tiragolumab and atezolizumab. OUTLINE: Patients are randomized to 1 of 4 groups. GROUP A: Patients receive atezolizumab intravenously (IV) over 60 minutes and tiragolumab IV over 20-75 minutes and 14-19 days later, undergo surgical resection. Following surgery, patients may receive tiragolumab IV and atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo magnetic resonance imaging (MRI) at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study. GROUP B: Patients receive tiragolumab IV over 20-75 minutes and 14-19 days later, undergo surgical resection. Following surgery, patients may receive tiragolumab IV and atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study. GROUP C: Patients receive atezolizumab IV over 60 minutes and 14-19 days later, undergo surgical resection. Following surgery patients may receive atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study. GROUP D: Patients undergo surgical resection on study. Following surgery patients may receive atezolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo MRI at baseline, 24-72 hours after surgery, then every 9 weeks until progression and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, and then every 3 months. ;