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    DRUG CLASS:

    KRAS G12D inhibitor

    Related drugs:
    4d
    A Study of TSN1611 Treating Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation (clinicaltrials.gov)
    P1/2, N=440, Recruiting, Tyligand Pharmaceuticals (Suzhou) Limited | N=150 --> 440
    Enrollment change
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    KRAS (KRAS proto-oncogene GTPase)
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    Erbitux (cetuximab) • paclitaxel • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium
    4d
    Co-targeting KRAS and Exportin1 as an effective therapeutic strategy for KRASG12D mutant pancreatic ductal adenocarcinoma. (PubMed, bioRxiv)
    Here, we demonstrate that the second-generation XPO1 inhibitor Eltanexor synergizes with MRTX1133 to enhance its efficacy in multiple PDAC models. By enhancing KRASG12D inhibitor activity and potentially reducing the required therapeutic dose, this combination approach offers a novel means to delay or overcome resistance. These findings provide a strong preclinical rationale for clinical trials evaluating KRAS inhibitors in combination with XPO1 inhibitors and may significantly improve outcomes for a substantial subset of PDAC patients who currently lack effective targeted treatment options.
    Journal • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • CCND1 (Cyclin D1) • XPO1 (Exportin 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • DUSP6 (Dual specificity phosphatase 6)
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    KRAS mutation • KRAS G12D • KRAS G12
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    MRTX1133 • eltanexor (KPT-8602)
    8d
    HDAC5 deficiency induces intrinsic resistance to KRAS inhibition by disrupting c-Myc acetylation-ubiquitination homeostasis. (PubMed, J Clin Invest)
    Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HDAC5 (Histone Deacetylase 5) • NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase)
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    KRAS mutation • KRAS G12D
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    MRTX1133
    14d
    Phase 1 Study to Investigate TCRTs KRAS Mutation in Unresectable, Advanced, and/or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=24, Recruiting, AstraZeneca | Trial completion date: Apr 2044 --> Nov 2043
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    16d
    Phase III Study to Compare GFH375 and Chemotherapy in Patients With KRAS G12D-Mutant Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P3, N=320, Not yet recruiting, Genfleet Therapeutics (Shanghai) Inc.
    New P3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    gemcitabine • paclitaxel • 5-fluorouracil • irinotecan • leucovorin calcium • Teysuno (gimeracil/oteracil/tegafur)
    17d
    A Study of GFH375 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors Harboring KRAS G12D Mutation (clinicaltrials.gov)
    P1/2, N=126, Recruiting, Genfleet Therapeutics (Shanghai) Inc.
    New P1/2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Erbitux (cetuximab) • gemcitabine • paclitaxel
    17d
    A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance. (PubMed, Proc Natl Acad Sci U S A)
    Likewise, a combination of selective inhibitors of KRAS (RMC-6236/daraxonrasib), EGFR family (afatinib), and STAT3 (SD36) induced the complete regression of orthotopic PDAC tumors with no evidence of tumor resistance for over 200 d posttreatment...Of importance, this combination therapy was well tolerated. In sum, these results should guide the development of new clinical trials that may benefit PDAC patients.
    Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
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    TP53 mutation • KRAS mutation
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    Gilotrif (afatinib) • MRTX1133 • daraxonrasib (RMC-6236)
    23d
    iEXPLORE: iExosomes in Treating Participants With Metastatic Pancreas Cancer With KrasG12D Mutation (clinicaltrials.gov)
    P1/2, N=28, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1 --> P1/2
    Phase classification
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12D • KRAS G12
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    Undisclosed MSC-derived Exosomes with KrasG12D siRNA
    23d
    A Study to Assess the Effect of Itraconazole, Rifampin, and Acid-Reducing Agents on INCB161734 Pharmacokinetics When Administered Orally in Healthy Participants (clinicaltrials.gov)
    P1, N=63, Completed, Incyte Corporation | Recruiting --> Completed
    Trial completion
    |
    itraconazole • rifampicin
    28d
    HRS-4642 in Combination With Nimotuzumab and Chemotherapy for BRPC With KRAS G12D Mutation (clinicaltrials.gov)
    P2, N=40, Not yet recruiting, Zhejiang University
    New P2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    paclitaxel • TheraCIM (nimotuzumab) • HRS-4642
    1m
    HRS 4642 Injection Combined With AG Versus Placebo Combined With AG Therapy in First-Line Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P3, N=588, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.
    New P3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    HRS-4642
    1m
    GFH375X1201: A Phase II Study to Evaluate GFH375 in Patients With KRAS G12D Mutant Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P2, N=0, Withdrawn, Genfleet Therapeutics (Shanghai) Inc. | N=83 --> 0 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2027 --> Aug 2027
    Enrollment change • Trial withdrawal • Trial primary completion date
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    KRAS (KRAS proto-oncogene GTPase)