This is a prospective, open-label single-arm, exploratory, two-stage design trial, aiming to investigate safety and efficacy of AK105 with anlotinib and radiotherapy adjuvant therapy in MGMT unmethylated newly diagnosed glioblastoma.
Glioblastoma is the most common and aggressive primary brain tumor in adults. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The Central Brain Tumor Registry of the United States (CBTRUS) Statistical Report primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016, glioblastoma accounted for 48.3% of primary malignant brain tumors. The Stupp protocol has become standard of care for the treatment of newly diagnosed GBM, however, some MGMT unmethylated glioblastomas are still resistant to temozolomide. Immunotherapy is being studied as treatment for the cancer, AK105 is a humanized monoclonal antibody that specially binds to PD-1. Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor. Based on the mechanism study, tumor vascular abnormalities promote tissue hypoxia and increase lactic acid, thereby activating immunosuppression and inhibiting T cell function. Anti-angiogenic drugs enhance the infiltration of effector immune cells by inducing normalization of blood vessels and reducing immunosuppression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Anlotinib a multi-target receptor tyrosine kinase inhibitor.
AK105 is a humanized monoclonal antibody that specifically binds to PD-1.
The radiotherapy regimen delivered 2.0Gy once a day, five days a week to a total dose of 60Gy.
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, China
RECRUITINGPFSR-6m
Progression-Free Survival rate at 6 months.
Time frame: up to 6 months
Progression-Free Survival(PFS)
PFS is defined as the time from randomization until the first documented progressive disease (PD) or death from any cause response assessment, based on Response Assessment in Neuro-Oncology (RANO) prior.
Time frame: up to approximately 24 months
Objective Response Rate(ORR)
ORR is defined as percentage of subjects confirmed complete response (CR) or partial response (PR), based on Response Assessment in Neuro-Oncology (RANO) prior to progression or any further therapy.
Time frame: up to approximately 24 months
Overall Survival(OS)
From the start of treatment to the date of death or the last follow-up.
Time frame: up to approximately 24 months
Disease Control Rate(DCR)
The DCR is defined as the proportion of subjects with CR, PR, or stable disease (SD), based on Response Assessment in Neuro-Oncology (RANO) prior.
Time frame: up to approximately 24 months
Safety
Observe any adverse events that occurred in all subjects during the clinical study and within 1 month after stopping the drug, including clinical symptoms, abnormal vital signs, and abnormalities in laboratory examinations, and record their clinical features, severity, and time of occurrence, duration, treatment methods and prognostic outcome, and determine its correlation with the study drug, based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0 to assess the safety.
Time frame: up to approximately 24 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.