^
    2d
    A Study to Evaluate the Mass Balance, Metabolism, Elimination, and Drug Levels of [14C]-BMS-986504 (MRTX1719) in Participants With Advanced Solid Tumors With Homozygous Methylthioadenosine Phosphorylase Deletion (clinicaltrials.gov)
    P1, N=8, Recruiting, Bristol-Myers Squibb | Trial completion date: Apr 2026 --> Oct 2027 | Trial primary completion date: Apr 2026 --> Oct 2027
    Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    navlimetostat (BMS-986504)
    7d
    A Study Comparing Navlimetostat (BMS-986504) in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine in Participants With Untreated Metastatic Pancreatic Ductal Adenocarcinoma With Homozygous MTAP Deletion (MountainTAP-30) (clinicaltrials.gov)
    P2/3, N=470, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS-986504)
    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)
    13d
    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)
    15d
    Structure-based discovery of a highly potent, selective, and brain-penetrant MTA-cooperative PRMT5 synthetic lethal inhibitor for the treatment of glioblastoma. (PubMed, Eur J Med Chem)
    Although several MTA-cooperative PRMT5 synthetic lethal inhibitors have been advanced into clinical trials, only one of them (TNG908) showed brain permeability in the preclinical evaluation but failed to achieve the anticipated therapeutic exposure levels in glioblastoma in clinical trials...More importantly, compound 21 achieved significant tumor growth inhibition in an orthotopic U87MG brain tumor model, supported by its enhanced distribution and penetration within brain tissue. These results indicate the potential clinical advantages of compound 21 for treating MTAP- deleted tumors and support its potential utility against intracranial malignancies.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    TNG908
    19d
    Use of Human Dose Prediction Metrics to Enable Discovery of AZD3470, an MTA-Cooperative PRMT5 Inhibitor in Clinical Evaluation. (PubMed, J Med Chem)
    Herein, we report our efforts to further optimize our previously reported in vivo tool compound 1 ("AZ-PRMT5i-1") toward a clinical candidate-quality profile, by addressing key shortcomings of this compound─limited aqueous solubility, low hERG receptor activity, and an unfavorable predicted human dose. The highest quality compounds in this series were identified by the use of a dose-to-human (D2H) automated model. These efforts resulted in the identification of 14, which shows the appropriate physicochemical properties, DMPK characteristics, and PRMT5-driven activity to be selected for progression into clinical studies.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    20d
    SELECTmeso A Trial for Patients With Relapsed Malignant Mesothelioma SELECTmeso1 A Trial of BMS-986504 in Patients With MTAP-deficient Relapsed Mesothelioma (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, University of Southampton
    New P2 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    navlimetostat (BMS-986504)
    23d
    BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion (clinicaltrials.gov)
    P1/2, N=72, Not yet recruiting, Northwestern University
    New P1/2 trial • Pan tumor
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    pemetrexed • navlimetostat (BMS-986504)
    23d
    The Discovery of TNG456: A Highly Potent, Selective, Brain-Penetrant MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP-Deleted Cancers. (PubMed, J Med Chem)
    Loss of MTAP leads to the accumulation of 5'-methylthioadenosine (MTA), which sensitizes tumor cells to inhibition of protein arginine methyltransferase 5 (PRMT5). Herein we describe the discovery of TNG456, a potent and highly selective MTA-cooperative PRMT5 inhibitor that is brain penetrant in preclinical species and currently in Phase I/II clinical studies for the treatment of advanced or metastatic solid tumors with MTAP loss, with a focus on glioblastoma.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    27d
    A Study to Investigate the Effect of the CYP3A Inducer Phenytoin and the CYP3A Inhibitor Itraconazole on the Pharmacokinetics of BGB-58067 in Healthy Participants (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, BeOne Medicines
    New P1 trial
    |
    itraconazole