A Single Center, Open-Label, Randomized Study to Evaluate the Safety and Efficacy of Neoadjuvant and Adjuvant Pembrolizumab on Top of Standard Chemo-Radiotherapy (Stupp Protocol) in Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme (GBM).

Brief Summary

Detailed Description

This is an open-label, Phase IV study of Pembrolizumab employed in neoadjuvant and adjuvant setting on top of standard therapy to evaluate the short-term and long-term safety, tolerability and efficacy in disease control in Glioblastoma Multiforme (GBM) patients. The control arm will be a group of patients treated in accordance with Standard of Care (SoC). The study will include 3 treatment arms (up to n=12 evaluable patients per arm) and will be conducted at single site in Poland. Patients with GBM will be randomly assigned in 1:1:1 ratio into one of 3 treatment arms: * Treatment arm 1 - n=12 evaluable patients - neoadjuvant Pembrolizumab (2 doses, 200mg each) plus adjuvant Pembrolizumab (16 cycles q3w, 200mg each) on top of standard chemo-radiotherapy (Stupp protocol: radiotherapy 60Gy over 6 weeks, 2 Gy per daily fraction Mo-Fri setting plus Temozolomide 75mg/m2 BSA daily during radiotherapy and six cycles post-radiotherapy of 150-200mg/m2 BSA for 5 days in each 28-day cycle) * Treatment arm 2 - n=12 evaluable patients - neoadjuvant Pembrolizumab (2 doses, 200mg each) on top of standard chemo-radiotherapy (Stupp protocol: radiotherapy 60Gy over 6 weeks, 2 Gy per daily fraction Mo-Fri setting plus Temozolomide 75mg/m2 BSA daily during radiotherapy and six cycles post-radiotherapy of 150-200mg/m2 BSA for 5 days in each 28-day cycle) * Treatment arm 3 - n=12 evaluable patients - standard chemo-radiotherapy (Stupp protocol: radiotherapy 60Gy over 6 weeks, 2 Gy per daily fraction Mo-Fri setting plus Temozolomide 75mg/m2 BSA daily during radiotherapy and six cycles post-radiotherapy of 150-200mg/m2 BSA for 5 days in each 28-day cycle) A pre-screening period will identify potential candidates for enrollment. Once qualified to the study patients will be randomized to one of the treatment arms. Then patients randomized to treatment arm 1 and 2 will receive first dose of neoadjuvant Pembrolizumab on day 4 and day 18 (200mg each). An immuno-PET scan for these arm 1 and 2 patients will be performed on day 29 and 30. Up to 72 hours after last immuno-PET scan all patients will undergo tumor resection. After surgery all patients will be treated in accordance with standard of care (Stupp protocol) with combined radio- and chemotherapy. Radiotherapy will consist of 60Gy over 6 weeks in daily fraction of 2Gy in Mo-Fri setting and parallel chemotherapy with Temozolomide of 75mg/m2 of BSA on a daily basis. After completion of radiotherapy the chemotherapy will continue for six cycles of 28 days with 150-200mg/m2 Temozolomide on days 1-5 of each cycle. In addition, patients randomized to arm 1 will receive 16 cycles of 21 days with Pembrolizumab treatment in adjuvant setting of 200mg/cycle. During treatment period all patients will be assessed every three months and MRI will be performed in order to evaluate disease status/response. After EOT patient's follow up period will continue for up to 3 years from initial resection with MRI assessment every 3 months. If progression/relapse is identified, patients will undergo a tumor resection or biopsy within 48 hours thereafter. All patients will then stay in follow up until the end of three years follow up period or death from any cause. The evaluation of safety, tolerability, and quality-of-life (QoL) will be based on adverse event reporting criteria (Common Terminology Criteria for Adverse Events - CTCAE/WHO Classification of Diseases - ICD10), ECOG status assessment, KPS assessment, EORTC - QLQ-C30 and EORTC-QLQ-BN20 scale. Clinical assessment will be based on Response Assessment in Neuro-Oncology (RANO). For patients treated with immunotherapy beyond onset of objective disease progression, the iRANO scale will be used within first 6 months of immunotherapy. Due to a significant risk of identifying other pathology than GBM (i.e. metastasic tumor) in post-surgery histopathology it is anticipated that up to additional 6 patients may be recruited in order to achieve planned number of evaluable patients.

Primary Outcomes

Secondary Outcomes

• Time-to-progression(3 years after initial tumor surgery)