a study on Glioblastoma
This is an open-label, non-randomized, multicenter Phase 2 study of MEDI4736 with three non-comparative cohorts: Cohort A: 37 subjects with newly diagnosed unmethylated MGMT GBM will receive MEDI4736 every 2 weeks in combination with standard radiotherapy. Cohort B: 30 bevacizumab-naïve subjects with recurrent GBM will receive MEDI4736 every 2 weeks as monotherapy. Cohort B2: 32 bevacizumab-naïve subjects with recurrent GBM will receive MEDI4736 every 2 weeks + bevacizumab every 2 weeks (10 mg/kg). Cohort B3: 32 bevacizumab-naïve subjects with recurrent GBM will receive MEDI4736 every 2 weeks + bevacizumab every 2 weeks (3 mg/kg). Cohort C: 17 bevacizumab-refractory subjects with recurrent GBM will receive MEDI4736 every 2 weeks in combination with continued bevacizumab.
Phase 2 Study to Evaluate the Clinical Efficacy and Safety of MEDI4736 in Patients With Glioblastoma (GBM)
Under some circumstances, the immune system may control or even eliminate tumors. MEDI4736 is an experimental antibody that is made in the laboratory. Antibodies stimulating the immune system have been developed for treatment of human cancers. The idea behind developing this type of experimental drug is that stimulating the immune system could be a different way of preventing cancer growth or killing cancer cells.
This study will also evaluate how much MEDI4736 is in the blood at various times, whether the immune system becomes activated following treatment and the effect of treatment on cancer.
In subjects with newly diagnosed GBM (Cohort A), MEDI4736 will be administered with standard treatment which includes radiation following surgery. The idea to add MEDI4736 to standard radiation is that the radiation will cause cell death and release tumor proteins which will increase the immune activity of MEDI4736.
Subjects with recurrent GBM and who have never been treated with Avastin (Cohort B), will receive MEDI4736 alone.
In Cohorts B2 and B3, subjects with recurrent GBM and who have never been treated with Avastin will receive MEDI2736 in combination with standard or low dose Avastin respectively.
Subjects with recurrent GBM and who have currently progressed on Avastin (Cohort C), will continue receiving Avastin in combination with MEDI4736. Avastin is another type of antibody that prevents the growth of blood vessels that feed the tumor. Despite Avastin being approved by the FDA for cancer based on tumor response, essentially all patients eventually progress due to resistance.
The idea to treat cancer with MEDI4736, with or without Avastin, is to identify alternative treatment options for cancer, by stimulating the immune system to prevent cancer growth.
Glioblastoma Immunotherapy T Cell PD-L1 MEDI4736 Radiation Radiotherapy GBM Bevacizumab Antibodies, Monoclonal
Open to people ages 18 years and up
Cohorts B, B2, B3 and C:
NOTE: Recurrence is defined as progression following therapy (i.e., chemotherapy;radiation). If the subject had a surgical resection for relapsed disease and no anti-tumor therapy was administered for up to 12 weeks, and the subject has further evidence of tumor growth or undergoes another resection, this will be considered as one episode of recurrence.
Cohorts A, B, B2, B3 and C:
At the time of Study Day 1, subjects must be at least 4 weeks since major surgical procedure, open biopsy, or significant traumatic injury; there should be no anticipation of need for major surgical procedure during the course of the study.
There should be no core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Study Day 1.
Adequate hematologic, renal and hepatic function, as defined below:
Urinary protein quantitative value of ≤ 30 mg/dL in urinalysis or ≤1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample.
Cohorts B2, B3 and C:
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