^
    3d
    A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov)
    P1/2, N=329, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=649 --> 329
    Enrollment closed • Enrollment change
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    docetaxel • AMG 193
    26d
    MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario. (PubMed, Cancer Res)
    MTA-cooperative PRMT5 inhibitors such as BMS-986504/MRTX1719 and AMG 193 target the PRMT5-MTA complex, while inhibitors of the SAM synthetase methionine adenosyl transferase 2A (MAT2A), such as IDE397, deprive PRMT5 of its methyl donor SAM. In this review article, we summarize the mechanisms of action, preclinical data, and clinical data available thus far for these novel classes of oncology precision medicine and discuss potential future directions relevant to MTAP deletion as a promising synthetic lethal vulnerability for cancer therapy.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    MTAP deletion
    |
    BMS‐986504 • IDE397 • AMG 193
    2ms
    A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov)
    P1/2, N=649, Recruiting, Amgen | Trial completion date: Nov 2028 --> Jun 2028 | Trial primary completion date: Dec 2026 --> Jul 2026
    Trial completion date • Trial primary completion date
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    docetaxel • AMG 193
    3ms
    A Phase 2 Study of AMG 193 in Participants With MTAP-deleted Advanced NSCLC (MTAPESTRY 201) (clinicaltrials.gov)
    P2, N=200, Recruiting, Amgen | Trial completion date: Sep 2029 --> Nov 2030 | Trial primary completion date: Sep 2027 --> Nov 2028
    Trial completion date • Trial primary completion date
    |
    AMG 193
    5ms
    A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103) (clinicaltrials.gov)
    P1, N=350, Recruiting, Amgen | N=188 --> 350
    Enrollment change
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • AMG 193 • daraxonrasib (RMC-6236)
    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=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 Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov)
    P1/2, N=649, Recruiting, Amgen | Trial completion date: Jun 2028 --> Nov 2028 | Trial primary completion date: Aug 2026 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    docetaxel • AMG 193
    10ms
    A Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 Alone or in Combination With Other Therapies in Subjects With Homozygous MTAP-Deletion Advanced Thoracic Tumors (Master Protocol) (ChiCTR2500095932)
    P=N/A, N=312, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci
    New trial
    |
    PD-L1 (Programmed death ligand 1) • MTAP (Methylthioadenosine Phosphorylase)
    |
    PD-L1 expression • MTAP deletion
    |
    Keytruda (pembrolizumab) • carboplatin • pemetrexed • AMG 193
    10ms
    Discovery of AMG 193, an MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP-Deleted Cancers. (PubMed, J Med Chem)
    Preclinical data indicate that AMG 193 is brain-penetrant. AMG 193 is currently in Phase I/II clinical trials for the treatment of advanced MTAP-deleted solid tumors.
    Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    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=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
    12ms
    A Study of AMG 193 in Subjects With Advanced MTAP-null Solid Tumors (clinicaltrials.gov)
    P1/2, N=649, Recruiting, Amgen | Trial completion date: Jan 2028 --> Jun 2028
    Trial completion date
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    docetaxel • AMG 193
    12ms
    A Phase 2 Study of AMG 193 in Participants With MTAP-deleted Advanced NSCLC (clinicaltrials.gov)
    P2, N=200, Recruiting, Amgen | Trial completion date: Feb 2029 --> Sep 2029 | Trial primary completion date: Feb 2027 --> Sep 2027
    Trial completion date • Trial primary completion date
    |
    AMG 193