ArticleNature medicine2025
Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03875820 (FRAME), which is not on this map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
FRAME: A Phase I Trial of the Combination of Defactinib (VS-6063) (FAK Inhibitor) and VS-6766 (RO5126766) (CH5126776) (a Dual RAF/MEK Inhibitor) in Patients With Advanced Solid Tumours
Who cites it
30 citing papers in PubMed.
- Avutometinib, Abemaciclib, and Fulvestrant in Patients with HR+/HER2- Metastatic Breast Cancer Previously Treated with CDK4/6 Inhibitor: A Single-Arm Phase I Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Review
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Hypoxia-activated PROTAC for dual inhibition of FAK and EGFR enables synergistic mechano-chemical cancer therapy.Neoplasia (New York, N.Y.) · 2026Article
- Simultaneous Estimation of Avutometinib and Defactinib in Rat Plasma by Using LC-MS/MS and Its Application to Pharmacokinetic Studies.Biomedical chromatography : BMC · 2026Article
- Vitronectin Enrichment in Prostate Cancer Liver Metastases Promotes Adhesion and Survival.Cancer research communications · 2026Article
- Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy.Advanced healthcare materials · 2026Article
- Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- A Phase II Trial of Defactinib Combined with Avutometinib in Patients with Metastatic Uveal Melanoma.Cancers · 2026Article
- Therapy-Driven Molecular Evolution of Bladder Cancer: Roles of Cellular Plasticity and Tumor Microenvironment.International journal of molecular sciences · 2026Review
- Targeting KRAS G12C in Rare Mesonephric Carcinoma of the Cervix: A Promising Response to Sotorasib.JCO precision oncology · 2026Article
- Nitrogen-containing FDA-approved drugs in 2025: synthesis, significance and therapeutic applications.RSC advances · 2026Review
- Spatial transcriptomics reveals a molecular tumor budding signature in head and neck cancer.Genome medicine · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Disarming cancer resistance: FAK as a therapeutic target.Trends in cancer · 2026Review
- Fluorine-containing FDA-approved small-molecule drugs in 2025: significance, synthetic insights, and therapeutic applications.RSC advances · 2026Review
- Prevalence of Halogens in 2025 FDA-Approved Drugs: Highlight on Suzetrigine, the First Nonopioid Painkiller in Decades.Journal of medicinal chemistry · 2026Article
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Use of signal transduction inhibitors as single agents to treat cancer leads to resistance because of the plasticity of intracellular signaling, and combination therapy can overcome this. We describe the first-in-human trial of avutometinib (RAF-MEK clamp) and defactinib (focal adhesion kinase inhibitor) in patients with solid tumors. The trial met its primary endpoint and recommended a phase 2 dose and schedule. The recommended phase 2 dose and schedule for a 28-day cycle was determined to be avutometinib 3.2 mg once a day, twice weekly (Monday and Thursday or Tuesday and Friday), and defactinib 200 mg twice a day, seven days a week. Both drugs were administered orally on a 3 weeks 'on' and 1 week 'off' basis. The pharmacokinetics and pharmacodynamics were consistent with previous reports of avutometinib and defactinib used as single agents. Key findings include an objective response rate of 42.3% (11 of 26; 95% confidence interval 23.4-63.1) and a median progression-free survival of 20.1 months (95% confidence interval 11.2-43.9) in patients with low-grade serous ovarian cancer. This study demonstrates the importance of intermittent dosing schedules in combined targeting of the mitogen-activated protein kinase and focal adhesion kinase pathways to improve tolerability, and has acquired proof of concept of anti-tumor activity against low-grade serous ovarian cancer, a tumor relatively resistant to chemotherapy. ClinicalTrials.gov identifier NCT03875820 .
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.