^
    10d
    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)
    26d
    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)
    28d
    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)
    1m
    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)
    1m
    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)
    2ms
    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
    3ms
    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 • navlimetostat (BMS‐986504)
    4ms
    Clinical Significance of MTAP Deletions and their Overlap with Concurrent Oncogenic Driver Alterations Including EGFR in Non-Small Cell Lung Cancer. (PubMed, J Thorac Oncol)
    MTAP dels frequently co-occur with oncogenic driver alterations and can develop at time of osimertinib resistance. A patient with oncogenic driver-positive, MTAP-del NSCLC had a partial response to PRMT5 inhibitor treatment. This work could inform future trials of PRMT5 and MAT2A inhibitors.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)
    |
    EGFR mutation • CDKN2A deletion • MTAP deletion
    |
    MSK-IMPACT
    |
    Tagrisso (osimertinib) • navlimetostat (BMS‐986504)
    4ms
    A Study to Assess Safety, Tolerability and Drug Levels of BMS-986504 in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=32, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open
    |
    navlimetostat (BMS‐986504)
    4ms
    CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov)
    P1, N=336, Recruiting, Bristol-Myers Squibb | Trial completion date: Apr 2026 --> Dec 2027 | Trial primary completion date: Apr 2026 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    navlimetostat (BMS‐986504)
    5ms
    PRIME: Clinical Trial to investigate the feasibility, safety, and tolerability of BMS-986504 in patients with recurrent MTAP-deleted Glioblastoma (ACTRN12625001238460)
    P2, N=10, Not yet recruiting, Peter MacCallum Cancer Centre
    New P2 trial
    |
    MGMT (6-O-methylguanine-DNA methyltransferase) • MTAP (Methylthioadenosine Phosphorylase)
    |
    navlimetostat (BMS‐986504)