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ONC201: a new treatment option being tested clinically for recurrent glioblastoma.

ABSTRACT: Glioblastoma is an aggressive central nervous system tumor with a 5-year-survival rate of less than 10%. Patients diagnosed with the disease are treated with surgery, radiation and temozolomide chemotherapy. Despite survival benefits, patients eventually relapse. There is a need for new treatments with improved efficacy. Imipridone ONC201 is a small molecule originally identified as a TNF-related apoptosis inducing ligand (TRAIL)-inducing compound. ONC201 has the unique ability to induce expression of both pro-death ligand TRAIL and its receptor DR5 through engagement of the cellular integrated stress response (ISR) pathway. Arrillaga-Romany et al. report early results from futility analysis of a phase II clinical trial of ONC201 in 17 patients with recurrent or refractory glioblastoma conducted at the Massachusetts General Hospital Cancer Center. The results are promising, as ONC201 shows preliminary signs of efficacy. Further testing of ONC201 in an expansion cohort of patients with glioblastoma is ongoing.

SUBMITTER: Ralff MD

PROVIDER: S-EPMC6117120 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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ONC201: a new treatment option being tested clinically for recurrent glioblastoma.

Ralff Marie D MD Lulla Amriti R AR Wagner Jessica J El-Deiry Wafik S WS

Translational cancer research 20171001 Suppl 7

Glioblastoma is an aggressive central nervous system tumor with a 5-year-survival rate of less than 10%. Patients diagnosed with the disease are treated with surgery, radiation and temozolomide chemotherapy. Despite survival benefits, patients eventually relapse. There is a need for new treatments with improved efficacy. Imipridone ONC201 is a small molecule originally identified as a TNF-related apoptosis inducing ligand (TRAIL)-inducing compound. ONC201 has the unique ability to induce express ...[more]

PMID: 30175049

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Project description:IntroductionPsoriatic arthritis (PsA) is an immune-mediated chronic inflammatory arthropathy associated with impaired physical function and reduced quality of life. Biologic therapies that target tumor necrosis factor (anti-TNF) have significantly improved clinical outcomes. Partial, non- and transient responses remain common comprising significant unmet clinical need. New therapies with novel modes of action are urgently required.ObjectivesThe interleukin (IL)-17 pathway has recently been attributed a critical role in the pathogenesis of spondyloarthritides. Herein, we review data from clinical studies with secukinumab, a novel fully human IgG1κ anti-IL-17A monoclonal antibody (mAb), in patients with active PsA.ResultsAcross two pivotal phase 3 studies, secukinumab provided significant and sustained reductions in the signs and symptoms of PsA, inhibition of radiographic progression, and improved patient-reported outcomes and measures of quality of life. The primary efficacy endpoint, a ≥20% improvement from baseline according to the American College of Rheumatology 20 (ACR20) response at Week 24, was significantly higher in patients treated with secukinumab compared with placebo, with improvements sustained through at least 52 weeks. Clinical benefits were seen with secukinumab regardless of concomitant methotrexate treatment and in patients who were either anti-TNF-naïve or who were inadequate responders to anti-TNF therapy. Secukinumab was well-tolerated, with a safety profile consistent with that previously reported in psoriasis trials. The most common adverse events were nasopharyngitis, upper respiratory tract infections, and headache.ConclusionSecukinumab offers an effective new addition to the available treatment options for PsA. Regulatory submissions have been filed worldwide, with the first approvals recently obtained in Japan and Europe. Future studies are required to define the optimal timing and strategic use of this novel treatment modality.FundingNovartis Pharma.

Dataset Information

ONC201: a new treatment option being tested clinically for recurrent glioblastoma.

Publications

ONC201: a new treatment option being tested clinically for recurrent glioblastoma.

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