^
    5d
    Quantitative Global Proteomics of Formalin-Fixed Paraffin-Embedded Tumors Identifies Dimethylated G3BP1 at Arginine 460 as a Robust Pharmacodynamic Biomarker of Methylthioadenosine Phosphorylase-Selective Protein Arginine Methyltransferase 5 Inhibition. (PubMed, J Proteome Res)
    We evaluated 145 DMA peptides in xenograft models treated by a novel MTAP-selective PRMT5 inhibitor, AZD3470...Using this quantitative assay, more than 90% reduction in G3BP1(R460) modification at 100 mg/kg was reproducibly detected in MTAP-null xenograft models. Our findings suggested that the DIA-MS proteomics assay can provide high specificity and sensitivity in the detection of PRMT5 inhibition.
    PK/PD data • Journal
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    MTAP (Methylthioadenosine Phosphorylase) • G3BP1 (G3BP Stress Granule Assembly Factor 1)
    7d
    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, Recruiting, BeOne Medicines | Not yet recruiting --> Recruiting
    Enrollment open
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    itraconazole
    7d
    CA240-0008: [14C]-BMS986504 Mass Balance Study in Patients with Advanced Solid Tumors with Homozygous MTAP Deletion (2024-515518-41-00)
    P1, N=16, Recruiting, Bristol-Myers Squibb Services Unlimited Company
    New P1 trial
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    navlimetostat (BMS-986504)
    8d
    Safety and Efficacy of BMS-986504 in Unresectable Malignant Peripheral Nerve Sheath Tumor (clinicaltrials.gov)
    P1/2, N=17, Not yet recruiting, Ankit Mangla, MD | Initiation date: Apr 2026 --> Aug 2026
    Trial initiation date
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    navlimetostat (BMS-986504)
    14d
    PRMT5-mediated methylation of LKB1 controls PD-L1 expression in NSCLC. (PubMed, Biomed J)
    These findings identify a PRMT5-LKB1-AMPK regulatory axis controlling PD-L1 expression in a cell-context-dependent manner and suggest that LKB1 status may serve as a predictive biomarker for combining PRMT5 inhibitors with ICB in NSCLC. This strategy offers a potential therapeutic avenue to overcome immunotherapy resistance in LKB1-proficient NSCLC.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • PRMT5 (Protein Arginine Methyltransferase 5)
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    PD-L1 expression
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    pemrametostat (GSK3326595) • onametostat (JNJ-64619178)
    16d
    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)
    21d
    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
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    gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS-986504)
    23d
    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
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    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium • anvumetostat (AMG 193) • daraxonrasib (RMC-6236)
    27d
    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)
    27d
    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)
    27d
    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)
    29d
    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
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    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
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    TNG908