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    A phase I study to evaluate the safety, pharmacokinetics, and pharmacodynamics of PF-06939999 (PRMT5 inhibitor) in patients with selected advanced or metastatic tumors with high incidence of splicing factor gene mutations. (PubMed, ESMO Open)
    PF-06939999 demonstrated a tolerable safety profile and objective clinical responses in a subset of patients, suggesting that PRMT5 is an interesting cancer target with clinical validation. However, no predictive biomarker was identified. The role of PRMT5 in cancer biology is complex and requires further preclinical, mechanistic investigation to identify predictive biomarkers for patient selection.
    P1 data • PK/PD data • Journal • Metastases
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    PRMT5 (Protein Arginine Methyltransferase 5)
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    PF-06939999
    3years
    SAM Competitive PRMT5 Inhibitor PF-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated NSCLC with Decreased Liability of Drug Resistance. (PubMed, Mol Cancer Ther)
    Drug sensitivity to PF-06939999 in NSCLC cells associates with cancer pathways including MYC, cell cycle and spliceosome, and with mutations in splicing factors such as RBM10. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 in the treatment of splicing dysregulated NSCLC.
    Journal
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    RBM10 (RNA Binding Motif Protein 10) • PRMT5 (Protein Arginine Methyltransferase 5)
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    PF-06939999
    over3years
    [VIRTUAL] PF‑06939999, a potent and selective PRMT5 inhibitor, in patients with advanced or metastatic solid tumors: A phase 1 dose escalation study. (ASCO 2021)
    PF-06939999 showed dose-dependent and manageable toxicities in this phase 1 dose escalation study . Objective tumor responses were observed in pts with HNSCC and NSCLC . Analysis of archival tissue for the presence of splicing factor mutations and other potential predictive biomarkers is ongoing .
    Clinical • P1 data
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    PRMT5 (Protein Arginine Methyltransferase 5)
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    PF-06939999