^
    1d
    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)
    4d
    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
    7d
    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)
    |
    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)
    7d
    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)
    29d
    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)
    1m
    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)
    2ms
    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)
    2ms
    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)
    2ms
    CA240-0029: A Study of BMS-986504 in Combination with Pembrolizumab Plus Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer with Homozygous MTAP Deletion (2025-521511-40-00)
    P2/3, N=191, Recruiting, Bristol-Myers Squibb Services Unlimited Company
    New P2/3 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • paclitaxel • albumin-bound paclitaxel • pemetrexed • navlimetostat (BMS-986504)
    2ms
    CA240-0030: A study of BMS-986504 in combination with Nab-p/Gem versus placebo in combination with Nab-p/Gem in untreated metastatic PDAC with homozygous MTAP deletion (2025-522598-12-00)
    P2/3, N=162, Recruiting, Bristol-Myers Squibb Services Unlimited Company
    New P2/3 trial
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    |
    gemcitabine • albumin-bound paclitaxel • navlimetostat (BMS-986504)
    3ms
    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) • navlimetostat (BMS-986504)
    3ms
    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
    |
    IDE397 • navlimetostat (BMS-986504) • AMG 193