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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:
    24d
    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)
    1m
    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)
    1m
    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)
    1m
    Properties of FDA-approved small molecule protein kinase inhibitors: a 2026 update. (PubMed, Pharmacol Res)
    The following ten drugs received FDA approval in 2025 - avutometinib (inhibiting MEK1/2 in serous ovarian carcinomas), defactinib (blocking FAK in low grade serous ovarian carcinomas), delgocitinib (antagonizing the JAK family in hand eczema), mirdametinib (inhibiting MEK1/2 in type I neurofibromatosis), remibrutinib (blocking BTK in chronic spontaneous urticaria), rilzabrutinib (antagonizing BTK in chronic immune thrombocytopenia), sunvozertinib (blocking mutant exon 21 insertion EGFR NSCLC), taletrectinib (inhibiting mutant ROS1 in NSCLC), vimseltinib (blocking CSF1R in tenosynovial giant cell tumors), and zongertinib (antagonizing mutant HER2 in NSCLC). This article summarizes the physicochemical properties of all 94 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 45 of the 94 FDA-approved drugs have a least one Lipinski rule of five violation.
    FDA event • Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CSF1R (Colony stimulating factor 1 receptor)
    |
    EGFR mutation
    |
    Gomekli (mirdametinib) • Avmapki (avutometinib) • Hernexeos (zongertinib) • Fakzynja (defactinib) • Ibtrozi (taletrectinib) • Zegfrovy (sunvozertinib) • Rhapsido (remibrutinib) • Romvimza (vimseltinib)
    2ms
    Long lasting response to the combination of Avutometinib and Defactinib after progression on Binimetinib in a patient with recurrent low grade serous ovarian carcinoma - A case report. (PubMed, Gynecol Oncol Rep)
    The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • MUC16 (Mucin 16, Cell Surface Associated)
    |
    KRAS mutation
    |
    Mektovi (binimetinib) • Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    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
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    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
    |
    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)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • RAS mutation • HRAS mutation
    |
    everolimus • Avmapki (avutometinib) • Fakzynja (defactinib)
    2ms
    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
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    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
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)
    3ms
    Therapeutic advances and molecular insights in low-grade serous ovarian carcinoma. (PubMed, Bull Cancer)
    MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.
    Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    Mekinist (trametinib) • 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 | Trial completion date: Oct 2026 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    Avmapki (avutometinib) • Fakzynja (defactinib)