BMS‐986504 / BMS 
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  • ||||||||||  BMS?986504 / BMS
    CA240-0007: BMS-986504 With Anti-PD-1 or Chemotherapy as Treatment for Advanced Solid Tumors With Homozygous MTAP Deletion (Exhibit Hall Rows 28-36) -  Jul 22, 2025 - Abstract #IASLCWCLC2025IASLC_WCLC_2035;    
    P1
    Exclusion criteria specific to the PDAC substudy include a history of select lung diseases, connective tissue disorders, peripheral artery disease, chronic leukemias, or the ongoing need for warfarin or for a treatment known to inhibit or induce cytochrome P450 3A4 or 2C8 that cannot be switched to an alternative treatment prior to study entry...Further substudies with BMS-986504 combination regimens are planned. The combination substudies are currently recruiting, and approximately 155 patients will be enrolled across all substudies.
  • ||||||||||  MTAPloss Is Frequent and Potentially Targetable With PRMT5 Inhibitors in Oncogene-Driven NSCL (Exhibit Hall) -  Jul 22, 2025 - Abstract #IASLCWCLC2025IASLC_WCLC_1874;    
    MRTX1719 monotherapy showed IC50 <0.5 ?M in 5/7 EGFR + MTAP -deleted models, and <0.16 ?M in all 5 ALK + MTAP -deleted lines...Preclinical data suggest that oncogene-driven tumors with MTAP loss are sensitive to single agent PRMT5 inhibitors and that combination TKI and PRMT5 inhibitors may have additive or synergistic antitumor activity. These findings support clinical testing of combined TKI and PRMT5 inhibitors in oncogene-driven MTAP deleted NSCLC.
  • ||||||||||  BMS?986504 / BMS
    Trial completion date, Trial primary completion date:  Clinical Trial of BMS-986504 in Recurrent GBM Patients (clinicaltrials.gov) -  May 14, 2025   
    P1,  N=9, Recruiting, 
    Abstract is embargoed at this time. Trial completion date: Jun 2027 --> Sep 2027 | Trial primary completion date: Jun 2026 --> Sep 2026
  • ||||||||||  BMS?986504 / BMS
    Enrollment open:  Clinical Trial of BMS-986504 in Recurrent GBM Patients (clinicaltrials.gov) -  Apr 14, 2025   
    P1,  N=9, Recruiting, 
    These results support further investigation of BMS-986504 at 400 and 600 mg QD as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP-del. Not yet recruiting --> Recruiting
  • ||||||||||  pemrametostat (GSK3326595) / Ipsen, BMS?986504 / BMS
    Preclinical evaluation of drugs for the treatment of MTAP-deficient cancers (Section 21; Poster Board No: 6) -  Mar 25, 2025 - Abstract #AACR2025AACR_9207;    
    This selective PRMT5 inhibitor developed a superior anti-tumor effect, achieving a tumor growth inhibition of over 100% after three weeks of treatment. In summary, our findings may advance the development of novel therapeutic strategies for MTAP-deficient cancers.
  • ||||||||||  pemrametostat (GSK3326595) / Ipsen, BMS?986504 / BMS
    Developing PRMT5 inhibition-based Immuno-oncology combination therapies in MTAP-loss tumors (Section 28; Poster Board No: 28) -  Mar 25, 2025 - Abstract #AACR2025AACR_5273;    
    The combination also increased CD8+ T cell proliferation in MTAP-KO tumor tissues. Collectively, our results provide a strong rationale for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors.
  • ||||||||||  TNG456 / Tango Therap
    TNG456 is a next-generation, brain-penetrant, MTA-cooperative PRMT5 inhibitor for the treatment of solid tumors with MTAP loss (Section 20; Poster Board No: 23) -  Mar 25, 2025 - Abstract #AACR2025AACR_3155;    
    Oral administration of TNG456 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in multiple cell line- and patient-derived xenograft models. With enhanced potency and selectivity for MTAP-null cancer cells, and strong preclinical evidence of brain-penetrance, TNG456 has the potential for broad clinical activity in MTAP-null solid tumors including gliomas and CNS metastases.
  • ||||||||||  OncoKBTM, MSK's precision oncology knowledge base: 2024 updates (Section 46; Poster Board No: 6) -  Mar 25, 2025 - Abstract #AACR2025AACR_2632;    
    Additionally, OncoKB included KRAS G12C in colorectal cancer and IDH1 mutations in myelodysplastic syndromes as Level 1 following FDA approval of adagrasib + cetuximab and ivosidenib, respectively...Lastly, novel biomarkers including FBXW7 and PPP2R1A alterations (endometrial and ovarian cancer), SMARCA4 mutations (non-small cell lung cancer and esophageal adenocarcinoma) and MTAP deletions (all solid tumors) were included in OncoKB based on compelling preclinical and emerging clinical evidence in association with lunresertib + camonsertib, PRT3789, and AMG193 and MRTX1719, respectively...OncoKB also implemented major software updates to support data integration into the EPIC platform. Future OncoKB efforts are focused on whole genome/exome curation, inclusion of biomarkers for non-NGS-based precision oncology therapies, and the development of a clinical trial matching system.
  • ||||||||||  BMS?986504 / BMS
    Enrollment change:  CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov) -  Aug 19, 2024   
    P1/2,  N=580, Recruiting, 
    Collectively, our results provide a strong rationale and mechanistic insights for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors. N=370 --> 580
  • ||||||||||  MTAP deleted cancer targeting synthetic lethal therapeutic / Ryvu Therap
    Discovery of novel MTA-cooperative PRMT5 inhibitors as targeted therapeutics for MTAP-deleted cancers (Section 24) -  Mar 5, 2024 - Abstract #AACR2024AACR_6897;    
    The correlation between compound exposure and on-target effect was confirmed in PK/PD and efficacy studies. Taken together, these studies confirm that MTA cooperative PRMT5 inhibitors exert strong synthetic lethal phenotype in MTAP deleted cancers and offer an exciting therapeutic opportunity for a large patient population.
  • ||||||||||  MTAP loss alters the epigenetic landscape and demonstrates superior therapeutic sensitivity to concomitant PRMT5 and PARP inhibition in cholangiocarcinoma (Section 22) -  Mar 5, 2024 - Abstract #AACR2024AACR_6873;    
    P1/2
    This renders selective targeting of MTAP null tumors with agents (MRTX1719, AMG193, TNG462, TNG908) targeting MTA bound PRMT5 (PRMT5:MTA), while sparing surrounding normal MTAP wild-type (WT) tissue...To address this pressing need, we co-treated CCA cell lines with MRTX1719 and PARP inhibitor olaparib...Similar differences in proportion of splicing events were also observed in MTAP loss CCA patient derived xenografts as compared to WT models. Collectively, these data implicate MTAP to be a crucial player in modulation of the chromatin and splicing events that may drive therapeutic response to PRMT5 inhibition.
  • ||||||||||  BMS?986504 / BMS
    Trial completion date, Trial primary completion date:  CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov) -  Oct 6, 2023   
    P1/2,  N=370, Recruiting, 
    Early signs of clinical activity were observed including objective responses in patients with MTAP del melanoma, gallbladder adenocarcinoma, mesothelioma, non-small cell lung cancer, and MPNST from the Phase 1/2 study. Trial completion date: Jan 2024 --> Apr 2026 | Trial primary completion date: Jan 2024 --> Apr 2026
  • ||||||||||  MRTX1719 / Mirati
    Identification of mechanism-based combination targets effective with the MTA-cooperative PRMT5 inhibitor MRTX1719 for the treatment of MTAP deleted cancers (Section 18; Poster Board #2) -  Mar 14, 2023 - Abstract #AACR2023AACR_5005;    
    P1/2
    Further investigation into potential biomarkers conferring sensitivity or resistance to PRMT5 inhibition was also performed using orthogonal datasets including molecular characterization, differential expression, differential splicing and proteomic analysis. These data suggest MRTX1719, an MTA cooperative PRMT5 inhibitor currently in a Phase I clinical trial (NCT05245500), has the potential to be a synthetically lethal precision medicine for multiple indications harboring MTAP del with high unmet medical need either as a single agent or in combination with clinically feasible rational combination partners.
  • ||||||||||  MRTX1719 / Mirati
    Journal:  Atropisomeric Racemization Kinetics of MRTX1719 Using Chiral Solvating Agent-Assisted F NMR Spectroscopy. (Pubmed Central) -  Sep 21, 2022   
    Here, we describe use of the chiral phosphoric acid solvating agent (+)-TiPSY to resolve the signals of atropisomers in F NMR and to use the data to study the kinetics of racemization and determine the rotational energy barrier of clinical compound MRTX1719. This method is complimentary to traditional chiral high-performance liquid chromatography (HPLC) and enhances the toolkit for chiral analysis techniques.
  • ||||||||||  TNG462 / Tango Therap
    TNG462 is a potential best-in-class MTA-cooperative PRMT5 inhibitor for the treatment of peripheral MTAP-deleted solid tumors (Exhibition Hall) -  Sep 3, 2022 - Abstract #AACRNCIEORTC2022AACR_NCI_EORTC_370;    
    Oral administration of TNG462 drives dose-dependent antitumor activity including durable tumor regressions and complete responses in multiple cell line- and patient-derived xenograft models. With enhanced potency and selectivity for MTAP-deleted cancer cells, and optimized pharmacokinetic properties to extend target coverage, TNG462 has the potential for broader and deeper clinical activity in peripheral MTAP-deleted solid tumors.
  • ||||||||||  BMS?986504 / BMS
    Trial initiation date:  CA240-0007: Phase 1 Study of MRTX1719 in Solid Tumors With MTAP Deletion (clinicaltrials.gov) -  Apr 5, 2022   
    P1/2,  N=339, Recruiting, 
    With enhanced potency and selectivity for MTAP-deleted cancer cells, and optimized pharmacokinetic properties to extend target coverage, TNG462 has the potential for broader and deeper clinical activity in peripheral MTAP-deleted solid tumors. Initiation date: Feb 2022 --> May 2022