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Related Experiment Video

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AMG 193 Effective in Multiple Tumor Types

    Cancer Discovery
    |October 17, 2023
    PubMed
    Summary

    A phase I trial investigated the PRMT5 inhibitor AMG 193 in patients with MTAP-deleted solid tumors. Five patients experienced partial responses, demonstrating potential for this novel cancer therapy.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Pharmacology

    Background:

    • Methylthioadenosine (MTA) overproduction is common in cancers with methylthioadenosine phosphorylase (MTAP) gene deletions.
    • PRMT5 is a key enzyme in the arginine methylation pathway, and its inhibition is a therapeutic strategy for MTAP-deleted tumors.
    • Targeting PRMT5 aims to disrupt cancer cell growth and survival.

    Purpose of the Study:

    • To evaluate the safety and preliminary efficacy of AMG 193, a novel MTA-cooperative PRMT5 inhibitor.
    • To assess the response rate in patients with advanced MTAP-deleted solid tumors treated with AMG 193.
    • To identify tumor types that may benefit from PRMT5 inhibition.

    Main Methods:

    • Phase I clinical trial design.
    • Treatment with AMG 193 in patients with advanced MTAP-deleted solid tumors.

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  • Tumor response assessment using imaging scans post-treatment.

    • Main Results:

    • Partial responses were observed in 5 out of 39 patients (approximately 12.8%) with advanced MTAP-deleted solid tumors.
    • Responses were noted across diverse tumor types, including esophageal, pancreatic, renal cell, gallbladder, and ovarian Sertoli-Leydig cell cancers.
    • Preliminary data suggest a potential therapeutic window for PRMT5 inhibition in specific cancer contexts.

    Conclusions:

    • AMG 193 demonstrates preliminary anti-tumor activity in patients with MTAP-deleted solid tumors.
    • The observed responses across multiple tumor types warrant further investigation.
    • PRMT5 inhibition represents a promising targeted therapy approach for cancers with MTAP deletions.