^
    19d
    Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death. (PubMed, Blood Neoplasia)
    Interestingly, JNJ-64619178 upregulated death receptor 4 (DR4) and death receptor 5 (DR5) expression on the cell membrane of B-NHL cell lines, thereby sensitizing them, including the less BCL-2-dependent cell lines, to recombinant TRAIL-induced extrinsic apoptotic cell death. These findings highlight a role of PRMT5 in regulating both intrinsic and extrinsic apoptosis and suggest potential combination partners with PRMT5 inhibitors for potential clinical application in B-NHL.
    Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
    |
    onametostat (JNJ-64619178)
    23d
    A Study of PRMT5 Inhibitor BAY 3713372 in Participants With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=450, Recruiting, Bayer | Not yet recruiting --> Recruiting
    Enrollment open • First-in-human
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    1m
    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
    |
    MTAP (Methylthioadenosine Phosphorylase) • G3BP1 (G3BP Stress Granule Assembly Factor 1)
    1m
    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
    |
    itraconazole
    1m
    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
    |
    navlimetostat (BMS-986504)
    1m
    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
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    navlimetostat (BMS-986504)
    1m
    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
    |
    PD-L1 (Programmed death ligand 1) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • PRMT5 (Protein Arginine Methyltransferase 5)
    |
    PD-L1 expression
    |
    pemrametostat (GSK3326595) • onametostat (JNJ-64619178)
    1m
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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)