Serena Desideri

Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial

Michael Lim, Xiaobu Ye, Anna F. Piotrowski, ARATI DESAI et autres

Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the …

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Tumor Growth Rate (TGR) Analysis Predicts Survival in a Multicenter Phase II Study of the PARP Inhibitor Pamiparib (BGB-290) with Temozolomide in Recurrent IDH-Mutant Gliomas (ABTC-1801)

B. Ellingson, Timothy F. Cloughesy, Xiaobu Ye, Ashley Teraishi et autres

BACKGROUND AND PURPOSE: Mutations in isocitrate dehydrogenase (IDH) lead to production of the oncometabolite 2-hydroxygluterate (2-HG), which suppresses homologous recombination and induces poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Preclinical studies demonstrate that IDH-mutant gliomas are sensitive to PARP inhibition. Tumor growth rate …

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Phase I/II and window-of-opportunity study of pamiparib and metronomic temozolomide for recurrent isocitrate dehydrogenase mutant gliomas

David Schiff, Xiaobu Ye, Jing Li, Benjamin M. Ellingson et autres

BACKGROUND: Preclinical studies demonstrate activity of poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitors in isocitrate dehydrogenase (IDH) mutant gliomas. We investigated safety, tolerability, pharmacokinetics, and efficacy of the PARP inhibitor pamiparib in conjunction with metronomic low-dose temozolomide in patients with recurrent IDH mutant (IDHmt) …

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Data from Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma

Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko et autres

AbstractPurpose: Adavosertib is an oral small-molecule inhibitor of Wee1. The Adult Brain Tumor Consortium conducted a phase I study evaluating adavosertib in combination with radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM), as well as a surgical window-of-opportunity …

Supplementary Figure 1 from Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma

Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko et autres

Supplementary Figure 1. Differential expression analysis based on per-pixel adavosertib mass spectrometry imaging drug distribution (p-value = 0.115, t-test). Boxplot show the median, 25% and 75% quantiles.

Supplementary Table 1 from Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma

Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko et autres

Supplementary Table 1. Representativeness of Study Participants.

Supplementary Table 2 from Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma

Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko et autres

Supplementary Table 2. Estimated Pharmacokinetic values for AZD 1775.

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma

Verónica Rendo, Eudocia Q. Lee, Connor C. Bossi, Nicholas Khuu et autres

Inhibitors of murine double minute homolog 2 (MDM2) represent a promising therapeutic approach for the treatment of TP53 wild-type glioblastomas (GBMs), reactivating p53 signaling to induce cancer cell death. We conducted a surgical window-of-opportunity trial (NCT03107780) of the MDM2 inhibitor navtemadlin (KRT-232) …

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Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma

Eudocia Q. Lee, Brian M. Alexander, Carlos G. Romo, Jeffrey G. Supko et autres

PURPOSE: Adavosertib is an oral small-molecule inhibitor of Wee1. The Adult Brain Tumor Consortium conducted a phase I study evaluating adavosertib in combination with radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM), as well as a surgical window-of-opportunity …

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Assessing the dose of regadenoson required to transiently alter blood-brain barrier integrity in patients with infiltrating gliomas

Stuart A. Grossman, Carlos G. Romo, Xiaobu Ye, Brian G. Kral et autres

Abstract Background The blood-brain barrier (BBB) severely limits the delivery of therapeutic agents to the brain. Regadenoson, a Food and Drug Administration-approved adenosine A2 agonist, transiently increases BBB permeability in rodents to a 70 kDa dextran. This multi-institutional, NIH-funded study examined regadenoson’s …

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Phase I study of NT-I7, a long-acting interleukin-7, in severe treatment-related lymphopenia following standard radiation and temozolomide for high-grade glioma

Jian Campian, Stuart A. Grossman, Angela Shaulov Kask, Samuel Kosydar et autres

Abstract Background High-grade gliomas (HGG) have a poor prognosis despite aggressive treatment. Severe, persistent lymphopenia occurring in HGG patients after concurrent chemoradiation is associated with worse survival. NT-I7, a long-acting interleukin-7 analog, has been shown to increase CD4 and CD8 counts in …

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Surgical window of opportunity trial reveals mechanisms of response and resistance to navtemadlin (KRT-232) in patients with recurrent glioblastoma

Verónica Rendo, Eudocia Q. Lee, Connor C. Bossi, Nicholas Khuu et autres

Abstract We investigated the effectiveness of navtemadlin (KRT-232) in treating recurrent glioblastoma. A surgical window-of-opportunity trial ( NCT03107780 ) was conducted on 21 patients to determine achievable drug concentrations within tumor tissue and examine mechanisms of response and resistance. Both 120 mg …

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