^
    3d
    Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, M.D. Anderson Cancer Center
    New P1 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    Lynparza (olaparib) • BMS‐986504
    5d
    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
    23d
    A Study of IDE892 as Monotherapy and Combination in MTAP-deleted Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=260, Recruiting, IDEAYA Biosciences | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    IDE397
    23d
    Exploring structural diversity and dynamic stability of small-molecule PRMT5 inhibitors through machine learning-based QSAR and molecular modelling. (PubMed, Mol Divers)
    Analysis of consensus QSAR models identified two highly active PRMT5 inhibitor candidates (CHEMBL4539612 and CHEMBL4577464), with high affinity for binding (- 13.5 to - 13.7 kcal/mol) to the PRMT5 active site and interactions similar to those of the known clinical PRMT5 inhibitor ONAMETOSTAT...Network pharmacology analysis indicated that PRMT5 and its interacting partners are mainly associated with histone arginine methylation and spliceosomal assembly, processes that are frequently dysregulated in MTAP-deficient cancers. These findings suggest CHEMBL4539612 and CHEMBL4577464 as promising scaffolds for the development of selective PRMT5 inhibitors in epigenetic cancer therapy.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    onametostat (JNJ-64619178)
    28d
    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
    1m
    Enhancing CD8+ T Cells Infiltration Through the Protein Arginine Methyltransferase 5 (PRMT5)/CXCL10 Axis Restricts Cervical Cancer Progression. (PubMed, Biomolecules)
    Furthermore, the therapeutic efficacy of the selective PRMT5 inhibitor EPZ015666 was evaluated in a cervical cancer xenograft mouse model...In summary, these findings elucidate a novel mechanism whereby PRMT5 depletion in cervical cancer cells triggers a CXCL10-mediated chemotactic response, enhancing CD8+ T cell infiltration and restricting tumor progression. Thus, our study provides compelling evidence supporting the potential targeting of PRMT5 as a viable immunotherapeutic strategy for cervical cancer.
    Journal
    |
    CD8 (cluster of differentiation 8) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCR3 (C-X-C Motif Chemokine Receptor 3)
    |
    EPZ015666
    1m
    An Investigational Study of BGB-58067 As a Single Agent and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=244, Recruiting, BeOne Medicines | Trial completion date: Jun 2027 --> Jan 2029 | Trial primary completion date: Jun 2027 --> Jan 2029
    Trial completion date • Trial primary completion date
    2ms
    CR108485: A Study of JNJ-64619178, an Inhibitor of PRMT5 in Participants With Advanced Solid Tumors, NHL, and Lower Risk MDS (clinicaltrials.gov)
    P1, N=114, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Sep 2025 | Trial primary completion date: Dec 2025 --> Sep 2025
    Trial completion • Trial completion date • Trial primary completion date • First-in-human
    |
    onametostat (JNJ-64619178)
    2ms
    ABSK131-101: A Early Study of ABSK131 in Patients With Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=266, Recruiting, Abbisko Therapeutics Co, Ltd
    New P1 trial • First-in-human
    2ms
    A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov)
    P2, N=60, Not yet recruiting, M.D. Anderson Cancer Center
    New P2 trial
    |
    gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • BMS‐986504
    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
    2ms
    Study to Evaluate the Safety, Tolerability & Efficacy of TNG462 in Combination in PDAC & NSCLC Patients (clinicaltrials.gov)
    P1/2, N=183, Recruiting, Tango Therapeutics, Inc. | N=133 --> 183
    Enrollment change
    |
    gemcitabine • albumin-bound paclitaxel • irinotecan • daraxonrasib (RMC-6236) • zoldonrasib (RMC-9805) • vopimetostat (TNG462)