^
    1d
    PRIMAVERA: AZD3470 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies. (clinicaltrials.gov)
    P1/2, N=161, Recruiting, AstraZeneca | N=110 --> 161 | Trial completion date: May 2026 --> Apr 2029 | Trial primary completion date: May 2026 --> Apr 2029
    Enrollment change • Trial completion date • Trial primary completion date
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    Keytruda (pembrolizumab)
    2d
    Manganese-potentiated cGAS-STING activation with ATM/PRMT5 inhibition remodels the immunosuppressive microenvironment in osteosarcoma via bone-targeted delivery. (PubMed, Bioact Mater)
    To overcome these hurdles, we developed a bone-targeted, glutathione (GSH)-responsive polymeric nanoparticle (NPALN/Mn-AP) that chelates manganese (Mn) and delivers an ATM inhibitor (AZD0156) and a PRMT5 inhibitor (GSK3326595). By functionalizing this nanoplatform with alendronate (ALN) into NPALN/Mn-AP, we achieve preferential accumulation in bone tumors...In vivo studies demonstrate that NPALN/Mn-AP significantly inhibits OS progression and boosts systemic immune responses. This dual-action, bone-specific nanotherapeutic platform synchronized DNA-repair inhibition and Mn-enhanced immune-stimulation, offering a promising new approach for effective osteosarcoma treatment.
    Journal
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    STING (stimulator of interferon response cGAMP interactor 1)
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    pemrametostat (GSK3326595) • AZD0156
    5d
    PRMT5 inhibition sensitizes B-cell lymphoma cells to ferroptosis. (PubMed, Leukemia)
    Notably, combined treatment with the PRMT5 inhibitor GSK3326595 and DMF synergistically enhances anti-tumor activity in a patient-derived xenograft (PDX) model. These findings reveal a previously unrecognized PRMT5-ATF5-SLC7A11 axis that drives ferroptosis resistance in B-cell lymphomas and provide a strong rationale for targeting PRMT5 to potentiate ferroptosis-based therapies in relapsed or refractory disease.
    Journal
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    PRMT5 (Protein Arginine Methyltransferase 5) • SLC7A11 (Solute Carrier Family 7 Member 11) • ATF4 (Activating Transcription Factor 4)
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    pemrametostat (GSK3326595)
    6d
    SURYA-1: First in Human, Dose Escalation, Dose Expansion Study of AUR105 (clinicaltrials.gov)
    P1, N=17, Terminated, Aurigene Discovery Technologies Limited | N=40 --> 17 | Recruiting --> Terminated; Patient recruitment problems.
    Enrollment change • Trial termination • First-in-human
    6d
    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)
    6d
    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
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    gemcitabine • albumin-bound paclitaxel • oxaliplatin • irinotecan • navlimetostat (BMS-986504)
    7d
    PRMT5 inhibition impairs Fanconi Anemia pathway-mediated homologous recombination and enhances the antitumor efficacy of Temozolomide in glioblastoma. (PubMed, Cell Death Dis)
    Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. Furthermore, compared to monotherapy, there was a significant reduction in the proliferation marker Ki-67, while the apoptosis marker cleaved caspase 3 and the DNA damage response marker γH2AX were upregulated. Collectively, these findings identify PRMT5 as a critical regulator of the FA pathway in glioblastoma and demonstrate that PRMT5 inhibition potentiates TMZ efficacy by disrupting FA-dependent homologous recombination repair, indicating that the combination of PRMT5 inhibition and TMZ could be a novel therapeutic strategy for glioblastoma.
    Journal
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    HRD (Homologous Recombination Deficiency) • CASP3 (Caspase 3) • PRMT5 (Protein Arginine Methyltransferase 5)
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    temozolomide • LLY-283
    7d
    TNG908-C101: Safety and Tolerability of TNG908 in Patients With MTAP-deleted Solid Tumors (clinicaltrials.gov)
    P1/2, N=110, Terminated, Tango Therapeutics, Inc. | N=192 --> 110 | Active, not recruiting --> Terminated; Sponsor Decision - Business Decisions
    Enrollment change • Trial termination • First-in-human
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    TNG908
    21d
    A Phase 1a/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of PRMT5 Inhibitor BGB-58067 Alone and in Combination with Anticancer Agents in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=63, Recruiting, BeOne Medicines | N=44 --> 63
    Enrollment change • First-in-human
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    MTAP (Methylthioadenosine Phosphorylase)
    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
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    MTAP (Methylthioadenosine Phosphorylase)
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    Opdivo (nivolumab) • carboplatin • gemcitabine • temozolomide • albumin-bound paclitaxel • pemetrexed • navlimetostat (BMS-986504) • Opdualag (nivolumab/relatlimab-rmbw) • daraxonrasib (RMC-6236) • pumitamig (BNT327)
    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)
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    MTAP deletion
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    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
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    MTAP (Methylthioadenosine Phosphorylase)
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    MTAP deletion
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    Lynparza (olaparib) • navlimetostat (BMS-986504)