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    DRUG:

    ifebemtinib (IN10018)

    i
    Other names: IN10018, BI-853520, N10018, BI 853520, IN 10018, N 10018, BI853520, IN-10018, N-10018
    Company:
    Boehringer Ingelheim, InxMed
    Drug class:
    FAK inhibitor
    Related drugs:
    2d
    Inhibition of Focal Adhesion Restricts Chemoresistance in Pancreatic Cancer by Targeting SLC7A11 Mediated Ferroptosis. (PubMed, Adv Sci (Weinh))
    Gemcitabine-based chemotherapy regimens have shown limited antitumor effects for PDAC, and combination targets are urgently needed to restrict chemoresistance. Mechanistically, the focal adhesion kinase (FAK) inhibitor (IN10018) could restrict chemoresistance to Gem of PDAC by targeting SLC7A11-mediated ferroptosis through PI3K-Akt signaling pathway. For tumor microenvironment, IN10018 reduced the abundance of mesenchymal components and enhanced CD8+ T cell infiltration.
    Journal
    |
    CD8 (cluster of differentiation 8) • SLC7A11 (Solute Carrier Family 7 Member 11)
    |
    gemcitabine • ifebemtinib (IN10018)
    26d
    IN10018 Combination Therapy in Previously-treated Solid Tumors (clinicaltrials.gov)
    P1/2, N=0, Withdrawn, InxMed (Shanghai) Co., Ltd. | N=72 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    Tevimbra (tislelizumab-jsgr) • albumin-bound paclitaxel • ifebemtinib (IN10018)
    28d
    a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=140, Active, not recruiting, InxMed (Shanghai) Co., Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Anfangning (garsorasib) • ifebemtinib (IN10018)
    2ms
    IN10018 in Combination With RNK08954 for the Treatment of KRASG12D Mutation-Positive Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=92, Recruiting, InxMed (Shanghai) Co., Ltd.
    New P1/2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12D • KRAS G12
    |
    ifebemtinib (IN10018)
    2ms
    Focal adhesion kinase inhibition enhances response to checkpoint immunotherapy in hepatocellular carcinoma. (PubMed, J Transl Int Med)
    These models were treated with FAK inhibitor IN10018 as monotherapy or in combination with anti-PD-1 immunotherapy...FAK inhibitors can enhance the sensitivity of HCC to anti-PD-1 therapy by inhibiting angiogenesis and fibrosis and promoting CD8+ T cell infiltration. This effect exceeds the efficacy of the current first-line treatment, highlighting FAK inhibition as a novel and promising therapeutic strategy for HCC.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • PTK2 (Protein Tyrosine Kinase 2)
    |
    KRAS G12D • KRAS G12
    |
    ifebemtinib (IN10018)
    3ms
    a Study to Evaluate the Safety and Efficacy of D-1553 Combined With IN10018 in KRAS G12C Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=140, Recruiting, InxMed (Shanghai) Co., Ltd. | Trial completion date: Dec 2026 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2027
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Anfangning (garsorasib) • ifebemtinib (IN10018)
    3ms
    A Phase 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov)
    P3, N=400, Recruiting, InxMed (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    cisplatin • carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Anfangning (garsorasib) • ifebemtinib (IN10018)
    3ms
    IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma (clinicaltrials.gov)
    P1, N=51, Completed, InxMed (Shanghai) Co., Ltd. | Active, not recruiting --> Completed | N=120 --> 51
    Trial completion • Enrollment change
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • NRAS Q61 • NRAS G12 • NRAS G13
    |
    Tecentriq (atezolizumab) • Cotellic (cobimetinib) • ifebemtinib (IN10018)
    5ms
    Ifebemtinib and paclitaxel synergistically inhibit the proliferation and metastasis of TNBC by blocking PI3K/Akt pathway through LSD1/PIK3IP1 axis. (PubMed, Sci Rep)
    By inhibiting FAK activation and upregulating PIK3IP1, Ifebemtinib and paclitaxel blocked the PI3K/Akt pathway, effectively suppressing TNBC proliferation and metastasis. Our findings suggest that FAK may serve as a potential therapeutic target for TNBC.
    Journal
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDH1 (Cadherin 1) • BAX (BCL2-associated X protein) • VIM (Vimentin) • CDH2 (Cadherin 2) • CDK1 (Cyclin-dependent kinase 1)
    |
    paclitaxel • ifebemtinib (IN10018)
    7ms
    IN10018 With Nab-Paclitaxel and Cadonilimab for Metastatic or Recurrent Gastric-Type Cervical Adenocarcinoma: Phase 2 Trial (clinicaltrials.gov)
    P2, N=25, Recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Feb 2025
    Enrollment open • Trial initiation date
    |
    albumin-bound paclitaxel • Kaitanni (cadonilimab) • ifebemtinib (IN10018)
    7ms
    Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy. (PubMed, bioRxiv)
    We show that focal adhesion kinase (FAK) inhibition with ifebemtinib or tumor genetic FAK knockout (KO) in syngeneic ovarian tumor models stimulated resident large peritoneal macrophages to express CXCL13 chemokine and promoted B cell infiltration. reveal that tumor FAK inhibition educates macrophages to express CXCL13 associated with B cell infiltration - highlighting a new therapeutic pathway linking FAK inhibition, omega-3 fatty acid containing exosomes, and macrophage mediated anti-tumor activation. Genetic or small molecule FAK inhibition enhances ovarian tumor B cell infiltrationTumor FAK inhibition stimulates GATA6+ macrophages to make CXCL13FAKi, pegylated doxorubicin and anti-TIGIT promote tertiary lymphoid structuresOmega-3 fatty acids stimulate human HGSOC ascites macrophages to make CXCL13.
    Journal • IO biomarker
    |
    TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • GATA6 (GATA Binding Protein 6)
    |
    doxorubicin hydrochloride • ifebemtinib (IN10018)
    7ms
    A Phase 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (clinicaltrials.gov)
    P3, N=400, Not yet recruiting, InxMed (Shanghai) Co., Ltd.
    New P3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    cisplatin • carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Anfangning (garsorasib) • ifebemtinib (IN10018)