^
    16d
    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) • BMS‐986504
    18d
    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
    |
    BMS‐986504
    24d
    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)
    |
    BMS‐986504
    27d
    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)
    |
    BMS‐986504
    30d
    A Phase 2 Study of AMG 193 in Participants With MTAP-deleted Advanced NSCLC (MTAPESTRY 201) (clinicaltrials.gov)
    P2, N=200, Recruiting, Amgen | Trial completion date: Sep 2029 --> Nov 2030 | Trial primary completion date: Sep 2027 --> Nov 2028
    Trial completion date • Trial primary completion date
    |
    AMG 193
    1m
    PARP inhibitor and PRMT5 inhibitor synergy is independent of BRCA1/2 and MTAP status in breast cancer cells. (PubMed, Sci Rep)
    This study investigates the effects of two classes of PRMT5 inhibitors, GSK3326595 and TNG908, on breast cancer cell lines with different BRCA1/2 statuses to evaluate their therapeutic potential and synergy with PARP inhibitors. These findings highlight the potential of combining PRMT5 inhibitors with PARP inhibitors in a wide range of cancers beyond BRCA1/2 and MTAP mutants. Further investigation is warranted to elucidate the underlying mechanisms of sensitization and the timing of cellular responses to PRMT5 inhibition.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MTAP (Methylthioadenosine Phosphorylase)
    |
    BRCA wild-type
    |
    TNG908 • pemrametostat (GSK3326595)
    2ms
    PRIMROSE: A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=234, Recruiting, AstraZeneca | Trial completion date: May 2026 --> Feb 2026 | Trial primary completion date: May 2026 --> Feb 2026
    Trial completion date • Trial primary completion date
    3ms
    A First-in-human Study to Learn How Safe BAY 3713372 is and How it Works in Participants With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=370, Recruiting, Bayer | Phase classification: P1 --> P1/2 | N=70 --> 370
    Phase classification • Enrollment change • First-in-human
    3ms
    PRMT5 Inhibition Hits a Nerve (Sheath Tumor): A Targeted Strategy for MPNSTs. (PubMed, Clin Cancer Res)
    PRMT5 inhibitors represent a promising therapeutic approach for multiple cancers, but their clinical development is hindered by toxicity to normal cells. Synthetic lethality approaches using MTAP-cooperative PRMT5 inhibitors offer a compelling strategy that selectively targets cancer cells in nerve sheath sarcomas and other MTAP-deleted tumors.
    Journal
    |
    MTAP (Methylthioadenosine Phosphorylase)
    |
    MTAP deletion
    3ms
    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 | Not yet recruiting --> Recruiting
    Enrollment open
    |
    gemcitabine • albumin-bound paclitaxel • BMS‐986504
    3ms
    MountainTAP-29: A Study to Compare the Combination of BMS-986504 With Pembrolizumab and Chemotherapy Versus Placebo Plus Pembrolizumab and Chemotherapy in First-line Metastatic Non-small Cell Lung Cancer Participants With Homozygous MTAP Deletion (clinicaltrials.gov)
    P2/3, N=590, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • albumin-bound paclitaxel • pemetrexed • BMS‐986504
    3ms
    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=237, Recruiting, BeiGene | N=92 --> 237 | Trial completion date: Nov 2026 --> Jun 2027 | Trial primary completion date: Nov 2026 --> Jun 2027
    Enrollment change • Trial completion date • Trial primary completion date