^
    1d
    Ph1/2 Trial Of Navlimetostat With Pumitamig In MTAP-Deficient Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=17, Not yet recruiting, M.D. Anderson Cancer Center
    New P1/2 trial
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MTAP (Methylthioadenosine Phosphorylase) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    navlimetostat (BMS-986504) • pumitamig (BNT327)
    10d
    Acquired resistance to the PRMT5 inhibitor confers collateral sensitivity to MEK inhibition in MTAP-null non-small cell lung cancer. (PubMed, bioRxiv)
    Here, we investigated mechanisms of acquired resistance to the MTA-cooperative PRMT5 inhibitor BMS-986504/MRTX1719 in MTAP-null non-small cell lung cancer (NSCLC) cells and sought to identify therapeutic vulnerabilities that emerge upon resistance...Instead, resistance was associated with collateral sensitivity to MEK inhibition and enrichment of MAPK-related transcriptional programs. Together, these findings identify MEK inhibition as an actionable collateral vulnerability in MTAP-null NSCLC cells that acquire resistance to PRMT5 inhibition.
    Preclinical • Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    navlimetostat (BMS-986504)
    13d
    A Study Comparing 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, Recruiting, Bristol-Myers Squibb
    Trial initiation date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS-986504)
    20d
    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
    New P1/2 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    navlimetostat (BMS-986504)
    21d
    A Phase 1 Study of Navlimetostat Tablet Formulations (clinicaltrials.gov)
    P1, N=64, Not yet recruiting, Bristol-Myers Squibb
    New P1 trial
    |
    navlimetostat (BMS-986504)
    24d
    Therapeutic vulnerabilities exposed by the 9p21 loss identified through multiparametric drug screening inform rational combination strategies. (PubMed, NPJ Precis Oncol)
    We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context...Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings.
    Journal
    |
    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    gemcitabine • cytarabine • methotrexate • navlimetostat (BMS-986504) • S095033
    27d
    A Study of BMS-986504 With Standard-of-Care Therapy for People With Solid Tumor Cancer (clinicaltrials.gov)
    P1, N=60, Recruiting, Memorial Sloan Kettering Cancer Center
    New P1 trial • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MTAP (Methylthioadenosine Phosphorylase)
    |
    HER-2 overexpression • MTAP deletion
    |
    MSK-IMPACT • PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • PD-L1 IHC 73-10 pharmDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • carboplatin • gemcitabine • 5-fluorouracil • oxaliplatin • leucovorin calcium • navlimetostat (BMS-986504)
    27d
    A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov)
    P2, N=60, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting
    Enrollment open
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • navlimetostat (BMS-986504)
    2ms
    A Study of BMS-986504 Monotherapy and in Combination With Other Agents in Participants With Advanced and/or Metastatic Solid Tumors With Homozygous MTAP Deletion (MountainTAP-5) (clinicaltrials.gov)
    P2, N=260, Not yet recruiting, Bristol-Myers Squibb
    New P2 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    Opdivo (nivolumab) • carboplatin • gemcitabine • temozolomide • albumin-bound paclitaxel • pemetrexed • navlimetostat (BMS-986504) • Opdualag (nivolumab/relatlimab-rmbw) • daraxonrasib (RMC-6236) • pumitamig (BNT327)
    2ms
    MTAP Loss Is Frequent in Oncogene-Driven NSCLC and May Confer Sensitivity to Combined PRMT5 Inhibitors and Targeted Therapies. (PubMed, Ann Oncol)
    MTAP loss is frequent in oncogene-driven NSCLC, particularly in ALK-, RET-, and EGFR-altered subtypes. MTA-cooperative PRMT5 inhibition demonstrates broad activity in MTAP-deleted, oncogene-driven models and, and may enhance targeted therapy efficacy in selected settings.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
    |
    EGFR mutation • ALK rearrangement • CDKN2A deletion • MTAP deletion
    |
    Xalkori (crizotinib) • Tagrisso (osimertinib) • Alecensa (alectinib) • navlimetostat (BMS-986504)
    3ms
    A Phase II Study Evaluating BMS-986504 in MTAP-deleted Pancreatic Cancer (clinicaltrials.gov)
    P2, N=60, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended
    Trial suspension
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • navlimetostat (BMS-986504)
    3ms
    Phase 1b Trial of BMS-986504 in Combination With Olaparib in Patients With MTAP Loss (clinicaltrials.gov)
    P1, N=36, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jun 2026 --> Feb 2026
    Enrollment open • Trial initiation date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    Lynparza (olaparib) • navlimetostat (BMS-986504)