marked.bio

RAF/MEK clamp · small molecule

avutometinib

9 active trials across 7 of our biomarkers, targeting RAF/MEK. 1 active approval for a biomarker on marked.bio.

Also known as VS-6766, RO5126766, CH5126766.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
avutometinib + defactinib
FDA, 2025
recurrent KRAS-mutated LGSOC after prior systemic therapy Label names 'KRAS-mutated' (a broader group that includes G12C). AA 08/05/2025; on FDA Ongoing accelerated approvals list. Source
Avmapki Fakzynja Co-packBroader labeldefactinib page 		KRAS G12C low-grade serous ovarian Approved 2025 accelerated Not approved

RAMP 201 single-arm, 57 patients
Response 44% (31-58)Lasting range 3.3-31.1 months

Serious side effects 32%Stopped for side effects 14%Fatal 3.6%

Trial details and side effects
Patients
KRAS-mutated recurrent low-grade serous ovarian cancer after prior systemic therapy (NCT04625270)
Most common side effects
nausea 74%, rash 72%, fatigue 72%, diarrhoea 68%, musculoskeletal pain 68%, oedema 67% (57 patients)
Notes
US label 2025 sections 6 and 14, plus FDA Drug Trials Snapshot for side-effect rates. Dose reductions for side effects in 44%. Accelerated approval.
Source
US label

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
KRAS G12C 7 12 Phase 1/2
KRAS G12D 6 10 Phase 2
ALK fusion 1 1 Phase 2
BRAF V600E 1 2 Phase 1/2
IDH1/2 mutation 1 1 Phase 1/2
NTRK1/2/3 fusion 1 1 Phase 2
RET fusion or mutation 1 1 Phase 2

Sponsors

Industry sponsors leading active biomarker-selected trials of avutometinib.

  1. Verastem 1

Trials

9 of 14 trials shown

  1. Defactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer

    Recruiting Phase 2 Emory University Started 2024Primary completion 2029-03 NCT06495125

    avutometinib FDAdefactinib FDAnivolumab

    COHORT A ONLY: Patients must have known KRAS mutation

    KRAS G12CKRAS G12DAdvanced Lung Adenocarcinoma, Refractory Lung Adenocarcinoma, Stage III Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8

  2. Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma

    Recruiting Phase 1/2 University of Utah Started 2024Primary completion 2028-01 NCT06194929

    defactinibavutometinibencorafenib FDA EU

    Cohort B: BRAF V600E or BRAF V600K

    BRAF V600ECutaneous Melanoma, Brain Metastases

  3. 5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours

    Recruiting Phase 1/2 Institute of Cancer Research, United Kingdom Started 2024Primary completion 2029-09 NCT06630260

    avutometinibdefactinibtemozolomide

    Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2/3 are not included)

    IDH1/2 mutationGlioblastoma Multiforme (GBM), Glioblastoma Multiform (Grade IV Astrocytoma), Diffuse Hemispheric Glioma, H3 G34-Mutant, Malignant Primary Gliomas

  4. A Study of Avutometinib and Defactinib in People With Thyroid Cancer

    Recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2023Primary completion 2027-08 NCT06007924

    avutometinib FDAdefactinib FDA

    …ecurrent tumor, or metastases) possess at least one of the following genetic alterations: RAS mutation, NF1 mutation, RET rearrangement, NTRK rearrangement, ALK rearrangement, Class 2 or 3 BRA…

    KRAS G12CKRAS G12DALK fusionRET fusion or mutationNTRK1/2/3 fusionThyroid Cancer

  5. A Phase 2 Study of Avutometinib (VS-6766) Plus Defactinib

    Recruiting Phase 2 University of Oklahoma Started 2023Primary completion 2027-12 NCT05512208

    avutometinib FDAdefactinib FDA

    Tumor with known RAS mutation, BRAF (type I, II, and/or III) mutation, NF-1 and/or RAS activation status determined fro…

    KRAS G12CKRAS G12DEndometrioid Cancer, Mucinous Ovarian Cancer, High Grade Serous Ovarian Cancer, Cervical Cancer

  6. Phase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients

    Active, not recruiting Phase 1/2 Verastem Started 2022Primary completion 2026-06 NCT05074810

    avutometinib FDAsotorasib FDA EUdefactinib FDA

    Known KRAS G12C mutation

    KRAS G12CNon Small Cell Lung Cancer, KRAS Activating Mutation

  7. Phase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer

    Recruiting Phase 1 M.D. Anderson Cancer Center Started 2026Primary completion 2028-08 NCT07318324

    avutometinib FDAdefactinib FDAeverolimus

    Participants must have histologically or cytologically confirmed recurrent RAS mutant endometrial cancer.

    KRAS G12CKRAS G12DPhase IB, Avutometinib, RAS Pathway, Endometrial

  8. A Study of Avutometinib for People With Solid Tumor Cancers

    Active, not recruiting Phase 1 Memorial Sloan Kettering Cancer Center Started 2023Primary completion 2029-10 NCT06104488

    avutometinib FDA

    …ase pathway alterations including but not limited to BRAF/ARAF/CRAF fusions or mutations, KRAS/NRAS/HRAS alterations, PTPN11 or SOS1/2 mutations and/or loss of function alterations in NF1.

    KRAS G12CKRAS G12DRefractory Cancer, CNS Tumors, CNS Tumor, Adult, CNS Tumor, Childhood

  9. Phase I Trial of Defactinib and VS-6766.

    Active, not recruiting Phase 1 Institute of Cancer Research, United Kingdom Started 2017Primary completion 2023-04 NCT03875820

    avutometinib FDAdefactinib FDA

    …lly or cytologically proven advanced non-small-cell lung cancer (NSCLC) with a documented KRAS mutation, refractory to conventional treatment, or for which no conventional therapy exists or is …

    KRAS G12CKRAS G12DNSCLC, Low Grade Serous Ovarian Cancer, Endometrioid Carcinoma, Pancreatic Cancer