The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Alex Lossos - One of the best experts on this subject based on the ideXlab platform.
-
Preliminary results of immune modulating antibody MDV9300 (Pidilizumab) treatment in children with diffuse intrinsic pontine glioma
Journal of Neuro-Oncology, 2017Co-Authors: Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Hagit Toledano, Michael WeintraubAbstract:Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (Pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study. Enrolled patients were started on biweekly 6 mg/kg MDV9300 after radiation completion. Treatment was continued until disease progression on imaging. Patients were followed biweekly for the occurrence of neurological deficit toxicities and side effects. Secondary endpoints were event free survival and overall survival. Of 13 children diagnosed with DIPG during the study period, nine were enrolled in the study. The patients underwent radiotherapy and none had chemotherapy. A total of 83 cycles of MDV9300 (range 2–16) were applied. The main side effects were neutropenia (CTCAE grade 1–3), mild to moderate fatigue, and acute elevation of blood pressure. Four patients died within 1 year of the diagnosis, another three died within 2 years and two children are still alive nearly 30 months from diagnosis, with stable disease. The median event free survival is 9.3 months (range 6.8–24) and the median overall survival is 15.6 months (range 6.9–28). Preliminary results demonstrate that MDV9300 treatment is safe and may be effective in the treatment of children with DIPG.
-
it 11a phase i ii clinical trial of ct 011 Pidilizumab in diffuse intrinsic pontine glioma and relapsed high grade glioma a preliminary report
Neuro-oncology, 2014Co-Authors: Iris Fried, Michael Weintraub, Tal Ben Ami, Roy Shen, Mony Benifla, Anat Mordechai, Alex LossosAbstract:BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) and relapsed high grade glioma (HGG) are incurable diseases with an event free survival of 6-8 months. Anti-Programmed Death 1 (anti-PD1) antibodies have recently emerged as a promising treatment modality in multiple cancer types. Clinical studies evaluating anti PD1 antibodies in the setting of primary brain tumors have not yet been reported. Pidilizumab (CureTech, Yavne, Israel) is an anti- PD1 humanized immunoglubulin G1 monoclonal antibody. This investigator-initiated clinical trial evaluates Pidilizumab in malignant gliomas (NCT01952769). METHODS: Patients older than 3 years treated with not more than 2mg/M2 of dexamethasone per day are included. Patients with newly diagnosed DIPG are recruited for biweekly Pidilizumab within the first month after completion of radiotherapy. Patients with HGG relapsed after standard treatment are recruited for biweekly Pidilizumab as an add-on therapy to bevacizumab within 3 months of recurrence. The study was opened in February 2014. RESULTS: To date, 6 patients have been enrolled: three with newly diagnosed DIPG, two with HGG and one with relapsed DIPG (bevacizumab + Pidilizumab). A total of 30 cycles of Pidilizumab (range 2- 14) have been administered. Treatment was well tolerated with transient fatigue as the main side effect. Administration of Pidilizumab less than 10 days after bevacizumab resulted in a grade 3 blood pressure elevation in one patient. This did not recur when the interval between agents was increased. One patient withdrew because of parents' decision. One patient with HGG progressed and died within 2.5 months from enrollment. Two patients had a significant tumor shrinkage along with clinical improvement. Scheduled imaging evaluation is pending in the rest. CONCLUSION: The trial is ongoing. This report is confined to schedule and initial enrollment results.
Iris Fried - One of the best experts on this subject based on the ideXlab platform.
-
Preliminary results of immune modulating antibody MDV9300 (Pidilizumab) treatment in children with diffuse intrinsic pontine glioma
Journal of Neuro-Oncology, 2017Co-Authors: Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Hagit Toledano, Michael WeintraubAbstract:Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (Pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study. Enrolled patients were started on biweekly 6 mg/kg MDV9300 after radiation completion. Treatment was continued until disease progression on imaging. Patients were followed biweekly for the occurrence of neurological deficit toxicities and side effects. Secondary endpoints were event free survival and overall survival. Of 13 children diagnosed with DIPG during the study period, nine were enrolled in the study. The patients underwent radiotherapy and none had chemotherapy. A total of 83 cycles of MDV9300 (range 2–16) were applied. The main side effects were neutropenia (CTCAE grade 1–3), mild to moderate fatigue, and acute elevation of blood pressure. Four patients died within 1 year of the diagnosis, another three died within 2 years and two children are still alive nearly 30 months from diagnosis, with stable disease. The median event free survival is 9.3 months (range 6.8–24) and the median overall survival is 15.6 months (range 6.9–28). Preliminary results demonstrate that MDV9300 treatment is safe and may be effective in the treatment of children with DIPG.
-
it 11a phase i ii clinical trial of ct 011 Pidilizumab in diffuse intrinsic pontine glioma and relapsed high grade glioma a preliminary report
Neuro-oncology, 2014Co-Authors: Iris Fried, Michael Weintraub, Tal Ben Ami, Roy Shen, Mony Benifla, Anat Mordechai, Alex LossosAbstract:BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) and relapsed high grade glioma (HGG) are incurable diseases with an event free survival of 6-8 months. Anti-Programmed Death 1 (anti-PD1) antibodies have recently emerged as a promising treatment modality in multiple cancer types. Clinical studies evaluating anti PD1 antibodies in the setting of primary brain tumors have not yet been reported. Pidilizumab (CureTech, Yavne, Israel) is an anti- PD1 humanized immunoglubulin G1 monoclonal antibody. This investigator-initiated clinical trial evaluates Pidilizumab in malignant gliomas (NCT01952769). METHODS: Patients older than 3 years treated with not more than 2mg/M2 of dexamethasone per day are included. Patients with newly diagnosed DIPG are recruited for biweekly Pidilizumab within the first month after completion of radiotherapy. Patients with HGG relapsed after standard treatment are recruited for biweekly Pidilizumab as an add-on therapy to bevacizumab within 3 months of recurrence. The study was opened in February 2014. RESULTS: To date, 6 patients have been enrolled: three with newly diagnosed DIPG, two with HGG and one with relapsed DIPG (bevacizumab + Pidilizumab). A total of 30 cycles of Pidilizumab (range 2- 14) have been administered. Treatment was well tolerated with transient fatigue as the main side effect. Administration of Pidilizumab less than 10 days after bevacizumab resulted in a grade 3 blood pressure elevation in one patient. This did not recur when the interval between agents was increased. One patient withdrew because of parents' decision. One patient with HGG progressed and died within 2.5 months from enrollment. Two patients had a significant tumor shrinkage along with clinical improvement. Scheduled imaging evaluation is pending in the rest. CONCLUSION: The trial is ongoing. This report is confined to schedule and initial enrollment results.
James Mason - One of the best experts on this subject based on the ideXlab platform.
-
disabling immune tolerance by programmed death 1 blockade with Pidilizumab after autologous hematopoietic stem cell transplantation for diffuse large b cell lymphoma results of an international phase ii trial
Journal of Clinical Oncology, 2013Co-Authors: Philippe Armand, Arnon Nagler, Edie Weller, Steven M Devine, David Avigan, Yibin Chen, Mark S Kaminski, Kent H Holland, Jane N Winter, James MasonAbstract:Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of Pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of Pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 3...
Michael Weintraub - One of the best experts on this subject based on the ideXlab platform.
-
Preliminary results of immune modulating antibody MDV9300 (Pidilizumab) treatment in children with diffuse intrinsic pontine glioma
Journal of Neuro-Oncology, 2017Co-Authors: Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Hagit Toledano, Michael WeintraubAbstract:Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (Pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study. Enrolled patients were started on biweekly 6 mg/kg MDV9300 after radiation completion. Treatment was continued until disease progression on imaging. Patients were followed biweekly for the occurrence of neurological deficit toxicities and side effects. Secondary endpoints were event free survival and overall survival. Of 13 children diagnosed with DIPG during the study period, nine were enrolled in the study. The patients underwent radiotherapy and none had chemotherapy. A total of 83 cycles of MDV9300 (range 2–16) were applied. The main side effects were neutropenia (CTCAE grade 1–3), mild to moderate fatigue, and acute elevation of blood pressure. Four patients died within 1 year of the diagnosis, another three died within 2 years and two children are still alive nearly 30 months from diagnosis, with stable disease. The median event free survival is 9.3 months (range 6.8–24) and the median overall survival is 15.6 months (range 6.9–28). Preliminary results demonstrate that MDV9300 treatment is safe and may be effective in the treatment of children with DIPG.
-
it 11a phase i ii clinical trial of ct 011 Pidilizumab in diffuse intrinsic pontine glioma and relapsed high grade glioma a preliminary report
Neuro-oncology, 2014Co-Authors: Iris Fried, Michael Weintraub, Tal Ben Ami, Roy Shen, Mony Benifla, Anat Mordechai, Alex LossosAbstract:BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) and relapsed high grade glioma (HGG) are incurable diseases with an event free survival of 6-8 months. Anti-Programmed Death 1 (anti-PD1) antibodies have recently emerged as a promising treatment modality in multiple cancer types. Clinical studies evaluating anti PD1 antibodies in the setting of primary brain tumors have not yet been reported. Pidilizumab (CureTech, Yavne, Israel) is an anti- PD1 humanized immunoglubulin G1 monoclonal antibody. This investigator-initiated clinical trial evaluates Pidilizumab in malignant gliomas (NCT01952769). METHODS: Patients older than 3 years treated with not more than 2mg/M2 of dexamethasone per day are included. Patients with newly diagnosed DIPG are recruited for biweekly Pidilizumab within the first month after completion of radiotherapy. Patients with HGG relapsed after standard treatment are recruited for biweekly Pidilizumab as an add-on therapy to bevacizumab within 3 months of recurrence. The study was opened in February 2014. RESULTS: To date, 6 patients have been enrolled: three with newly diagnosed DIPG, two with HGG and one with relapsed DIPG (bevacizumab + Pidilizumab). A total of 30 cycles of Pidilizumab (range 2- 14) have been administered. Treatment was well tolerated with transient fatigue as the main side effect. Administration of Pidilizumab less than 10 days after bevacizumab resulted in a grade 3 blood pressure elevation in one patient. This did not recur when the interval between agents was increased. One patient withdrew because of parents' decision. One patient with HGG progressed and died within 2.5 months from enrollment. Two patients had a significant tumor shrinkage along with clinical improvement. Scheduled imaging evaluation is pending in the rest. CONCLUSION: The trial is ongoing. This report is confined to schedule and initial enrollment results.
Joseph D Rosenblatt - One of the best experts on this subject based on the ideXlab platform.
-
regulatory b cells in anti tumor immunity
International Immunology, 2015Co-Authors: Yu Zhang, Nicolas Gallastegui, Joseph D RosenblattAbstract:Advances in understanding of the immune microenvironment have highlighted the role of immunosuppressive T cell, myeloid, dendritic and monocytic sub-populations in inhibition of the anti-tumor immune response. The role of B cells in modulating the immune response to solid tumors as well as lymphoid malignancies is less well understood. Murine models of autoimmune disease have defined B regulatory cell (Breg) subsets with immune suppressive activity, including B cell subsets that express IL-10, and transforming growth factor-β, which can facilitate T regulatory cell recruitment and expansion. Multiple murine tumor models point to the existence of similar immune suppressive B cell sub-populations that can migrate into tumor deposits and acquire an immune suppressive phenotype, which then leads to attenuation of the local anti-tumor immune response. Other murine models of viral or chemically induced skin carcinogenesis have identified a pivotal role for B cells in promoting inflammation and carcinogenesis. While many human solid tumors demonstrate significant B cell infiltration and/or tertiary lymphoid structure formation, the functional properties of tumor-infiltrating B cells and their effects on immunity are poorly understood. Recent successes in early Phase I/II trials using anti-checkpoint inhibitor antibodies such as nivolumab or Pidilizumab directed against PD-1 in the setting of Hodgkin's and non-Hodgkin's lymphomas validate the therapeutic utility of reversing B cell-mediated immune suppression. Further studies to define Breg subsets, and mechanisms of suppression, may provide new avenues for modulation of the immune response and meaningful therapeutic intervention in both lymphoid and solid tumors.