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    DRUG:

    IDE397

    i
    Other names: GSK 4362676, GSK-4362676, IDE 397, IDE-397, IDE397, GSK4362676, GSK’676, GSK676, GSK 676
    Company:
    Ideaya Biosci
    Drug class:
    MAT2A inhibitor
    Related drugs:
    19d
    A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=184, Recruiting, Amgen | Trial completion date: Dec 2026 --> Sep 2027
    Trial completion date • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    2ms
    A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=184, Recruiting, Amgen | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Nov 2025 --> Mar 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    6ms
    A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=184, Recruiting, Amgen | Trial completion date: Jul 2026 --> Dec 2026
    Trial completion date • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    IDE397 • AMG 193
    7ms
    Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion (clinicaltrials.gov)
    P1, N=180, Recruiting, IDEAYA Biosciences | N=130 --> 180 | Trial completion date: Jun 2024 --> Mar 2027 | Trial primary completion date: Dec 2023 --> Dec 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    paclitaxel • docetaxel • Trodelvy (sacituzumab govitecan-hziy) • IDE397
    12ms
    Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion (clinicaltrials.gov)
    P1, N=130, Recruiting, IDEAYA Biosciences | N=382 --> 130
    Enrollment change
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    paclitaxel • docetaxel • IDE397
    1year
    A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=184, Recruiting, Amgen | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    over1year
    A Phase 1/2 Study of AMG 193 in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=184, Not yet recruiting, Amgen
    New P1/2 trial • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    over1year
    MAT2A inhibition in MTAP-/- tumors confers mechanistic vulnerabilities to multiple clinically actionable synthetic lethal drug combinations (AACR 2023)
    Synergy between IDE397 and pemetrexed was of particular interest given mechanistic convergence of the methionine salvage and folate cycle pathways on nucleotide synthesis in the context of MTAP-/-. Collectively, these observations indicate that MAT2A inhibition can generate cell states in MTAP-/- tumor cells that are selectively vulnerable to approved chemotherapies and targeted therapies. These synergistic relationships may provide a predictive biomarker strategy for multiple IDE397 synthetic lethal combination therapies.
    Clinical • Synthetic lethality
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    CDKN2A deletion • MTAP deletion
    |
    pemetrexed • IDE397
    over1year
    Dual inhibition of MAT2A and PRMT5 delivers synergistic anti-tumor responses in preclinical models of MTAP-deleted cancer (AACR 2023)
    We noted synergistic antiproliferative effects when the potent and selective MAT2A inhibitor IDE397 was combined with any of multiple MTA-cooperative PRMT5 inhibitors in MTAPdel cell lines that exhibit sensitivity to each single agent...The potentiation of the antitumor response with the combination did not occur in the MTAPWT setting. Thus, combined inhibition of MAT2A and PRMT5 potentially offers a compelling dual synthetic lethal opportunity to address unmet need for the many patients afflicted with MTAPdel cancers.
    Preclinical
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    CDKN2A deletion • MTAP deletion
    |
    IDE397
    over2years
    A phase I study of synthetic lethal, IDE397 (MAT2A inhibitor) as a monotherapy and in combination with chemotherapy in advanced solid tumors harboring MTAP deletion (ESMO 2022)
    Primary endpoints include safety and tolerability, RP2D determination, investigator-assessed tumor response by RECIST v1.1. Enrollment in the monotherapy dose escalation is ongoing with clearance of the first 5 dose levels without DLT.
    P1 data • Combination therapy • Synthetic lethality
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    MTAP deletion
    |
    IDE397
    over2years
    Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion (clinicaltrials.gov)
    P1, N=382, Recruiting, IDEAYA Biosciences | N=40 --> 382 | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
    Enrollment change • Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    MTAP deletion
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • pemetrexed • IDE397
    over3years
    Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion (clinicaltrials.gov)
    P1, N=40, Recruiting, IDEAYA Biosciences
    Clinical • New P1 trial
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    MTAP deletion
    |
    IDE397
    over3years
    [VIRTUAL] MAT2A inhibitor, IDE397, displays broad anti-tumor activity across a panel of MTAP-deleted patient-derived xenografts (AACR 2021)
    Xenograft studies indicate that IDE397 exhibits anti-tumor activity as a single agent in MTAP-deleted CDX models and in MTAP-deleted PDX models of NSCLC, pancreatic, bladder, head and neck, esophageal and gastric cancer. This data supports the clinical evaluation of IDE397 across a wide range of solid tumor types with MTAP-deletion.
    Clinical
    |
    MTAP (Methylthioadenosine Phosphorylase) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    MTAP deletion
    |
    IDE397