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    DRUG:

    IDE397

    i
    Other names: IDE397, GSK4362676, GSK’676, GSK676, GSK 676, GSK 4362676, GSK-4362676, IDE 397, IDE-397
    Company:
    Ideaya Biosci
    Drug class:
    MAT2A inhibitor
    Related drugs:
    4ms
    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=53, Active, not recruiting, Amgen | Trial completion date: Aug 2025 --> Jan 2026 | Trial primary completion date: Aug 2025 --> Jan 2026
    Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    9ms
    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=53, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=184 --> 53 | Trial completion date: Feb 2027 --> Aug 2025
    Enrollment closed • Enrollment change • Trial completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    11ms
    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: Sep 2027 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    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 | Trial completion date: Dec 2026 --> Sep 2027
    Trial completion date • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • AMG 193
    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 | 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
    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, Recruiting, Amgen | Trial completion date: Jul 2026 --> Dec 2026
    Trial completion date • Combination therapy • Metastases
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    IDE397 • AMG 193
    over1year
    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
    almost2years
    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
    over2years
    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
    over2years
    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
    over2years
    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
    over2years
    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