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    DRUG CLASS:

    SOS1 inhibitor

    Related drugs:
    7d
    A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation) (clinicaltrials.gov)
    P1, N=71, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
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    Mekinist (trametinib) • BI 1701963
    28d
    A Phase I/II Study of HYP-6589 Monotherapy in Treating Advanced Solid Tumors and in Combination With Tyrosine Kinase Inhibitors in Treating Patients With Advanced NSCLC Positive for Driver Genes (clinicaltrials.gov)
    P1/2, N=115, Recruiting, Sichuan Huiyu Pharmaceutical Co., Ltd | Trial completion date: Jul 2026 --> Apr 2028 | Trial primary completion date: Jul 2026 --> Apr 2028
    Trial completion date • Trial primary completion date
    2ms
    Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma. (PubMed, Nat Commun)
    Notably, combination therapy with SOS1 inhibitor MRTX0902, Trametinib, and anti-PD-1 antibody effectively increased intratumoural CD8+ T cell infiltration and improved survival. Our study thus reveals that targeting wild-type KRAS signalling in combination with ICIs may serve as an effective treatment strategy for advanced HCC patients.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • CXCL9 (Chemokine (C-X-C motif) ligand 9)
    |
    KRAS wild-type • RAS wild-type
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    Mekinist (trametinib) • MRTX0902
    4ms
    A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway (clinicaltrials.gov)
    P1/2, N=228, Active, not recruiting, Mirati Therapeutics Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12
    |
    Krazati (adagrasib) • MRTX0902
    5ms
    A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation (clinicaltrials.gov)
    P1, N=104, Recruiting, Bayer | Trial completion date: Nov 2027 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Jul 2027
    Trial completion date • Trial primary completion date
    |
    Lumakras (sotorasib)
    6ms
    Development and biological evaluation of novel SOS1 inhibitors featuring 5,8-dihydropyrido[4,3-d]pyrimidin-7(6H)-one scaffold. (PubMed, Bioorg Med Chem Lett)
    Among these, A15f and B5a emerged as the most potent compounds comparable to BI-3406...Molecular docking revealed that these two compounds shared a conserved binding mode with SOS1, similar to the reported inhibitors. These findings provide foundation for further development of SOS1-targeted anticancer therapeutics and offer valuable insights for structural optimization of this novel class of inhibitors.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    BI-3406
    10ms
    A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation) (clinicaltrials.gov)
    P1, N=71, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Apr 2025 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Mekinist (trametinib) • BI 1701963
    10ms
    SOS1 inhibitor BI-3406 shows in vivo antitumor activity akin to genetic ablation and synergizes with a KRASG12D inhibitor in KRAS LUAD. (PubMed, Proc Natl Acad Sci U S A)
    Furthermore, markedly stronger, synergistic antitumor effects were observed upon concomitant treatment with BI-3406 and MRTX1133 in the same in vivo LUAD mouse model. Our data confirm SOS1 as an actionable therapy target in RAS-dependent cancers and suggest that BI-3406 treatment may yield clinical benefit both as monotherapy or as a potential combination partner for multiple RAS-targeting strategies.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12D
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    MRTX1133 • BI-3406
    1year
    Characterization of the BH1406 non-small cell lung cancer (NSCLC) cell line carrying an activating SOS1 mutation. (PubMed)
    Besides BAY-293, BH1406 cells proved to be sensitive to the SOS1 inhibitors MRTX0902 and BI-3406...Additionally, the PI3K inhibitor dactolisib, the GSK-3 inhibitor BI-5521 as well as the bromodomain protein-directed PROTAC ARV-771 inhibited the growth of BH1406 cells significantly and showed synergistic interaction with BAY-293...BH1406 cells represent a novel cellular model suitable for the molecular characterization of SOS1 druggability. Such rare oncogenic driver genes are not included in standard NGS panels and need to be detected by expanded assays like WES.
    Journal • Preclinical
    |
    Lung Cancer Mutation Panel
    |
    dactolisib (RTB101) • BI-3406 • MRTX0902
    1year
    Novel potent SOS1 inhibitors containing a tricyclic quinazoline scaffold: A joint view of experiments and simulations. (PubMed, Eur J Med Chem)
    Furthermore, molecular dynamic simulations have unveiled that the tricyclic quinazoline derivatives exhibit extensive interaction with Tyr884, a crucial residue for the recognition between SOS1 and KRAS. Our findings provide fresh insights into the design of future SOS1 inhibitors, paving the way for innovative therapeutic strategies.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    1year
    A Phase I Study of BAY3498264 Given Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation (clinicaltrials.gov)
    P1, N=104, Recruiting, Bayer | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Lumakras (sotorasib)
    1year
    A Study to Learn BAY3498264 When Given Alone or Together With Sotorasib in Participants Who Have Advanced Solid Cancers With Specific Genetic Changes Called KRASG12C Mutation (clinicaltrials.gov)
    P1, N=104, Not yet recruiting, Bayer
    New P1 trial • Metastases
    |
    Lumakras (sotorasib)