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    DRUG CLASS:

    Pyk2 inhibitor

    Related drugs:
    9d
    RAMP 203: Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients (clinicaltrials.gov)
    P1/2, N=153, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jun 2026
    Enrollment closed • Trial primary completion date
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    KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation • KRAS G12C • KRAS G12
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    Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)
    10d
    Inactivation of Focal Adhesion Kinase FAK Rapidly Abrogates Keratinocyte Entry in Mitosis via Rho-Associated Kinase, Resulting in Squamous Differentiation. (PubMed, FASEB J)
    To investigate whether FAK plays a role in this checkpoint, we inactivated the protein in normal human oral keratinocytes by specific shRNAs or by the specific inhibitor defactinib...Concomitant inhibition of FAK-downstream Rho-associated kinase (Rock) rescued mitotic progression. The results unveil a rapid Rock-dependent mitosis switch upon inactivation of FAK, inducing terminal differentiation, pointing at a mitotic automatic mechanism of epithelia to suppress suprabasal proliferation of precancerous cells.
    Journal
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    TP53 (Tumor protein P53)
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    Fakzynja (defactinib)
    15d
    Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer (clinicaltrials.gov)
    P1, N=31, Not yet recruiting, M.D. Anderson Cancer Center
    New P1 trial
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K2 (Mitogen-activated protein kinase kinase 2)
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    KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation • HRAS mutation
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    everolimus • Avmapki (avutometinib) • Fakzynja (defactinib)
    17d
    Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P2, N=36, Not yet recruiting, Washington University School of Medicine
    New P2 trial
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    Avmapki (avutometinib) • Fakzynja (defactinib)
    22d
    Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma (clinicaltrials.gov)
    P2, N=42, Active, not recruiting, Washington University School of Medicine | Trial primary completion date: Dec 2025 --> Apr 2026
    Trial primary completion date
    |
    Fakzynja (defactinib)
    1m
    RAMP201J: A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients (clinicaltrials.gov)
    P2, N=16, Active, not recruiting, Verastem, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
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    Avmapki (avutometinib) • Fakzynja (defactinib)
    1m
    Identification of Treatment Concentrations of Defactinib or VS-6766 for the Treatment of Patients With Glioblastoma (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Emory University | Trial completion date: Oct 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
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    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    Unmet needs and emerging therapeutics in low-grade serous ovarian carcinoma: from chemoresistance to precision medicine. (PubMed, Future Oncol)
    Notably, the recent US Food and Drug Administration approval of the avutometinib/defactinib combination for KRAS-mutated recurrent LGSOC marks a significant milestone in targeted therapy for this disease. Despite these advances, challenges remain in optimizing sequencing strategies and overcoming acquired resistance. This review addresses the importance of understanding the distinct pathophysiology of LGSOC, diagnostic challenges, limitations of conventional treatments, and evolving therapeutic approaches in LGSOC.
    Review • Journal
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    KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation
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    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    Targeting focal adhesion kinase inhibits cell migration and non-angiogenic vascularization in malignant breast cancer. (PubMed, Breast Cancer)
    FAK inhibition was shown to suppress non-angiogenic vascularization. Defactinib has the potential to serve as a novel treatment for malignant breast cancer which is resistant to conventional therapies.
    Journal
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    PTK2 (Protein Tyrosine Kinase 2)
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    Fakzynja (defactinib)
    3ms
    A critical role of FAK signaling in Rac1-driven melanoma cell resistance to MAPK pathway inhibition. (PubMed, Oncogene)
    Therefore, despite the pleiotropic mechanisms of Rac1-driven MAPKi resistance, we find that combined inhibition of RAF and MEK with the RAF/MEK clamp avutometinib and FAK with the FAK inhibitor defactinib is a promising approach for suppressing the growth of Rac1-driven melanoma cells. Thus, the avutometinib plus defactinib combination, which is currently being investigated for brain metastatic cutaneous melanoma may also have utility against Rac1-driven MAPKi-resistance in heavily pre-treated, advanced disease.
    Journal
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    BRAF (B-raf proto-oncogene) • RAC1 (Rac Family Small GTPase 1)
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    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    Identification of Treatment Concentrations of Defactinib or VS-6766 for the Treatment of Patients With Glioblastoma (clinicaltrials.gov)
    P1, N=14, Active, not recruiting, Emory University | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    4ms
    Stereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma (clinicaltrials.gov)
    P2, N=42, Active, not recruiting, Washington University School of Medicine | Trial primary completion date: Sep 2025 --> Dec 2025
    Trial primary completion date
    |
    Fakzynja (defactinib)