^
    10d
    A Study Evaluating Anvumetostat 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=120, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=350 --> 120 | Trial completion date: Feb 2029 --> Nov 2026 | Trial primary completion date: Feb 2027 --> Oct 2026
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    RAS mutation • MTAP deletion
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • anvumetostat (AMG 193) • daraxonrasib (RMC-6236)
    14d
    A Phase 2 Study of Anvumetostat in Participants With MTAP-deleted Advanced NSCLC (MTAPESTRY 201) (clinicaltrials.gov)
    P2, N=61, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=200 --> 61 | Trial completion date: Nov 2030 --> Nov 2026 | Trial primary completion date: Nov 2028 --> Oct 2026
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    anvumetostat (AMG 193)
    14d
    Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104). (clinicaltrials.gov)
    P1, N=49, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=500 --> 49 | Trial completion date: Oct 2031 --> Nov 2026 | Trial primary completion date: Oct 2028 --> Oct 2026
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • MTAP (Methylthioadenosine Phosphorylase)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • MTAP deletion • KRAS G12
    |
    Keytruda (pembrolizumab) • carboplatin • paclitaxel • Lumakras (sotorasib) • pemetrexed • anvumetostat (AMG 193)
    14d
    A Study of Anvumetostat in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101) (clinicaltrials.gov)
    P1/2, N=329, Active, not recruiting, Amgen | Trial completion date: May 2028 --> Nov 2026 | Trial primary completion date: May 2026 --> Nov 2026
    Trial completion date • Trial primary completion date
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    docetaxel • anvumetostat (AMG 193)
    2ms
    A Phase 1/2 Study of Anvumetostat in Combination With IDE397 in Participants With Advanced Methylthioadenosine Phosphorylase (MTAP)-Null Solid Tumors (clinicaltrials.gov)
    P1/2, N=53, Completed, Amgen | Active, not recruiting --> Completed
    Trial completion
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397 • anvumetostat (AMG 193)
    4ms
    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 • anvumetostat (AMG 193)
    5ms
    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
    |
    IDE397 • navlimetostat (BMS-986504) • anvumetostat (AMG 193)
    6ms
    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 • anvumetostat (AMG 193)
    7ms
    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
    |
    anvumetostat (AMG 193)
    10ms
    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 • anvumetostat (AMG 193) • daraxonrasib (RMC-6236)
    10ms
    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 • anvumetostat (AMG 193)
    1year
    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 • anvumetostat (AMG 193)