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    Home > Active Ingredient News > Antitumor Therapy > Courier's inhibition of the RAS pathway can also affect protein degradation, and initial clinical results of innovative therapies for fatal brain cancer are positive

    Courier's inhibition of the RAS pathway can also affect protein degradation, and initial clinical results of innovative therapies for fatal brain cancer are positive

    • Last Update: 2021-11-13
    • Source: Internet
    • Author: User
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    ▎Editor of WuXi AppTec's content team On November 4, 2021, Chimerix announced that ONC201, an investigational therapy with a dual mechanism of action, has achieved positive top-line results in clinical trials for the treatment of recurrent gliomas
    .

    ONC201 is an oral small molecule dopamine receptor D2 (DRD2) antagonist and casein protease (ClpP) agonist for the treatment of patients with relapsed glioma with H3 K27M mutation
    .

    Recurrent high-grade glioma is a type of brain cancer, and the prognosis of pediatric patients with H3 K27M is particularly poor
    .

    ONC201 targets DRD2 and ClpP at the same time, blocking DRD2 can inhibit the RAS signaling pathway, and activating ClpP can promote the degradation of proteins in the mitochondria of cells that are related to the survival of cancer cells
    .

    The combination of these two effects can selectively induce tumor cell apoptosis
    .

    At present, the US FDA has granted ONC201 the fast-track qualification for the treatment of adult recurrent H3 K27M mutant high-grade glioma, the qualification for the treatment of rare pediatric diseases of H3 K27M mutant glioma, and the treatment of glioblastoma and malignant glioblastoma Orphan drug eligibility for tumors
    .

     ▲ Mechanism of action of ONC201 (picture source: reference [2]) The 50 patients whose efficacy can be evaluated in this trial have diffuse midline gliomas, which carry the H3 K27M mutation.
    Although they have received radiotherapy, the disease still progresses
    .

    The test results show that ONC201 makes the patient's overall response rate (ORR) reach 20.
    0% (95% CI: 10.
    0-33.
    7%)
    .

    The median duration of response (mDOR) reached 11.
    2 months (95% CI: 3.
    8-NE)
    .

    In terms of safety, the complete safety data collection and analysis of the cohort are in progress, and one serious adverse event was attributed to ONC201
    .

    The most frequently reported adverse events were nausea/vomiting, fatigue, and decreased lymphocyte counts
    .

    The complete data analysis results will be announced at the annual meeting of the Society of Neuro-Oncology (SNO) on November 20, 2021
    .

    "For these patients who do not have effective systemic treatment options, these data are exciting
    .

    " The researcher of this clinical study, Dr.
    Isabel Arrillaga-Romany, the director of neuro-oncology clinical trials at Massachusetts General Hospital, said, "In anticipation of the disease.
    The long-lasting response in the rapidly advancing patient population is impressive
    .

    "Reference: [1] Chimerix Announces Positive Topline Results for ONC201 in Recurrent H3 K27M-mutant Glioma.
    Retrieved November 4, 2021, from https://ir.
    chimerix.
    com/news-releases/news-release-details/chimerix -announces-positive-topline-results-onc201-recurrent-h3[2] Chimerix 3Q21 Corporate Presentation.
    Retrieved November 4, 2021, from https://ir.
    chimerix.
    com/static-files/cb22dcec-f4b4-4311-8e27 -42e393fbb5f9 Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
    .

    This article is for information exchange purposes only.
    The views in the article do not represent WuXi AppTec's position, nor does it mean that WuXi AppTec supports or opposes the views
    in the
    article .
    This article also It is not a treatment plan recommendation
    .

    If you need treatment plan guidance, please go to a regular hospital for treatment
    .

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