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    5ms
    5-methylthioadenosine phosphorylase (MTAP) loss in clinically advanced uveal melanoma (CAUM): A comprehensive genomic profiling (CGP) study (ESMO 2024)
    Treatment options are limited to Tebentafusp in patients with HLA-A*02:01 mutation with immunotherapy and chemotherapy yielding poor results...In a recent phase I trial of a PRMT5 inhibitor, PRT811, clinical activity was described in cases of CAUM. 676 CAUM and 9666 CASM patients underwent hybrid capture based CGP to evaluate genomic alterations (GA)... Although MTAP loss is less frequent in CAUM than in CASM, the recent evidence that this genomic alteration predicts responsiveness to PRMT5 inhibition is noteworthy. This highlights the importance of further investigating this biomarker for patients with this rare and clinically aggressive type of cancer.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Metastases
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    PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q) • HLA-A (Major Histocompatibility Complex, Class I, A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • GNA11 (G Protein Subunit Alpha 11) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    PD-L1 expression • MSI-H/dMMR • PD-L1 overexpression • BRAF mutation • HLA-A*02
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    PD-L1 IHC 22C3 pharmDx
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    Kimmtrak (tebentafusp-tebn) • P-500
    over1year
    A phase 1 study of the protein arginine methyltransferase 5 (PRMT5) brain-penetrant inhibitor PRT811 in patients (pts) with recurrent high-grade glioma or uveal melanoma (UM). (ASCO 2023)
    PRT811 demonstrated an acceptable safety profile and clinical activity in pts with glioma and MUM. Clinical trial information: NCT04089449.
    Clinical • P1 data
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • PRMT5 (Protein Arginine Methyltransferase 5)
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    P-500
    over2years
    Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review. (PubMed, J Immunother Precis Oncol)
    Partial response has been seen in adenoid cystic carcinoma from both GSK3326595 and JNJ-64619178, with four cases of stable disease seen with PRT543. Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811...Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.
    Review • Journal • IO biomarker
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • PRMT5 (Protein Arginine Methyltransferase 5)
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    IDH1 mutation
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    P-500 • PRT543 • pemrametostat (GSK3326595) • onametostat (JNJ-64619178)
    3years
    [VIRTUAL] A phase 1 dose escalation study of protein arginine methyltransferase 5 (PRMT5) brain penetrant inhibitor PRT811 in patients with advanced solid tumors, including recurrent high- grade gliomas (AACR-NCI-EORTC 2021)
    No abstract available
    Clinical • P1 data
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    PRMT5 (Protein Arginine Methyltransferase 5)
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    P-500