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    DRUG:

    Avmapki (avutometinib)

    i
    Other names: VS-6766, RG7304, RO5126766, CKI27, RG 7304, CH-5126766, CKI-27, R-7304, RG-7304, RO-5126766, CK127, CH 5127566, CH5126766, VS 6766, RO 5126766, VS6766
    Company:
    Roche, Verastem
    Drug class:
    MEK inhibitor, BRAF inhibitor, cRAF inhibitor
    Related drugs:
    3d
    A Study of Avutometinib for People With Solid Tumor Cancers (clinicaltrials.gov)
    P1, N=3, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=23 --> 3
    Enrollment closed • Enrollment change
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    An evaluation of avutometinib in combination with defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer. (PubMed, Expert Rev Anticancer Ther)
    Avutometinib plus defactinib represents a promising targeted therapeutic strategy for recurrent LGSOC, particularly in patients with KRAS-mutant tumors. If confirmed in phase III trials, this combination may establish a molecularly informed disease-specific treatment paradigm with the potential for more durable disease control than existing therapies.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    Avutometinib and defactinib: a novel dual pathway inhibition strategy for recurrent KRAS-mutant low-grade serous ovarian cancer. (PubMed, Int J Gynecol Cancer)
    The authors discuss adverse event management and the implications for integration into routine clinical practice. Clinicians caring for patients with low-grade serous ovarian carcinoma can use the drug knowledge and evidence outlined in this review to assist with implementing avutometinib and defactinib therapy.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    Stereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov)
    P2, N=36, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=50, Recruiting, Emory University | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029
    Trial completion date • Trial primary completion date • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
    |
    KRAS G12C • KRAS G12
    |
    Opdivo (nivolumab) • Avmapki (avutometinib) • Fakzynja (defactinib) • ABP 206 (nivolumab biosimilar)
    3ms
    FRAME: Phase I Trial of Defactinib and VS-6766. (clinicaltrials.gov)
    P1, N=87, Active, not recruiting, Institute of Cancer Research, United Kingdom | Trial completion date: Oct 2023 --> Oct 2026
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • RAS (Rat Sarcoma Virus)
    |
    KRAS mutation • RAS mutation • KRAS G12
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    Disarming cancer resistance: FAK as a therapeutic target. (PubMed, Trends Cancer)
    The FDA recently granted accelerated approval of the small-molecule focal adhesion kinase (FAK) inhibitor (FAKi, defactinib) in combination with a RAF-MEK clamp inhibitor (avutometinib) for KRAS-mutated low-grade serous ovarian cancer developed by Verastem Inc. In this study, we review a short history of FAK, summarize ongoing combinatorial clinical trials, discuss potential mechanisms of action, and highlight studies showing that FAK activation is a chemo- and mechano-sensitive signaling hub driving tumor adaptive changes. Targeting FAK disarms tumor resistance through multiple mechanisms, which supports new biological insights and future clinical combinations.
    Review • Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    4ms
    Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer (clinicaltrials.gov)
    P2, N=33, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2028 --> Feb 2029 | Trial primary completion date: Feb 2026 --> Feb 2029
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • BRAF V600 • BRAF wild-type
    |
    Erbitux (cetuximab) • Avmapki (avutometinib) • Fakzynja (defactinib)
    5ms
    DDU RAF/MEK: Phase I Trial of VS-6766 Alone and in Combination With Everolimus (clinicaltrials.gov)
    P1, N=104, Completed, Royal Marsden NHS Foundation Trust | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Jun 2025 --> Oct 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation
    |
    everolimus • Avmapki (avutometinib)
    5ms
    A Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer (clinicaltrials.gov)
    P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)