^
    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
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    MTAP (Methylthioadenosine Phosphorylase)
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    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
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS-986504)
    19d
    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
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    MTAP (Methylthioadenosine Phosphorylase)
    |
    navlimetostat (BMS-986504)
    22d
    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
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    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
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    pemetrexed • navlimetostat (BMS-986504)
    27d
    A Phase 1 Study of Navlimetostat Tablet Formulations (clinicaltrials.gov)
    P1, N=64, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open
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    navlimetostat (BMS-986504)
    29d
    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
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MTAP (Methylthioadenosine Phosphorylase) • NTRK (Neurotrophic receptor tyrosine kinase)
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    navlimetostat (BMS-986504) • pumitamig (BNT327)
    1m
    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
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    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    navlimetostat (BMS-986504)
    1m
    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)
    2ms
    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)
    2ms
    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)
    2ms
    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
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    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
    2ms
    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
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MTAP (Methylthioadenosine Phosphorylase)
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    HER-2 overexpression • MTAP deletion
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    MSK-IMPACT • PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • PD-L1 IHC 73-10 pharmDx
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    Opdivo (nivolumab) • Yervoy (ipilimumab) • carboplatin • gemcitabine • 5-fluorouracil • oxaliplatin • leucovorin calcium • navlimetostat (BMS-986504)