Trial reportNature medicine2025
YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial.
Trial report 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 NCT04665206 (Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors), which is not on this map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors
Who cites it
44 citing papers in PubMed.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- First-in-human phase Ia study of the covalent TEAD palmitoylation inhibitor BPI-460372 in patients with advanced solid tumors: pharmacokinetics, exposure-limited dosing, and early antitumor activity.Biomarker research · 2026Article
- YAP and WWTR1/TAZ Connect Mechanotransduction and Mitochondrial Metabolism in Cardiac Hypertrophy and Ventricular Remodeling.Journal of cardiovascular translational research · 2026Review
- Hippo Pathway-YAP/TAZ Signaling: Molecular Mechanisms, Biological Function, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Advancing clinical trials for rare renal cell carcinoma subtypes: Consensus statements from the International Kidney Cancer Symposium North America 2025 think tank.Urologic oncology · 2026Article
- Extracellular matrix reprogramming by the YAP/TAZ/TGF-β2 axis drives immune exclusion in cholangiocarcinoma models.The Journal of clinical investigation · 2026Article
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Early targeting of the YAP/TEAD-PKC-NF-κB axis alleviates post-traumatic osteoarthritis.iScience · 2026Article
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Marine-Derived Fungal Metabolite MHO7 Promotes Breast Cancer Apoptosis as a Hippo Pathway Regulator by Modulating the YAP-TEAD Axis.Marine drugs · 2026Article
- Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The emerging role of the Hippo signaling pathway in interorgan crosstalk.The FEBS journal · 2026Review
- EDNRA Forms a Positive Feedback Loop with the Hippo/YAP Axis to Drive Triple-Negative Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brief report: attitudes and barriers toward genetic testing in pleural mesothelioma: a nationwide Italian survey.Familial cancer · 2026Article
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity.Med (New York, N.Y.) · 2026Article
- Prognostic impact of somatic mutations among patients with pleural and peritoneal mesothelioma.NPJ precision oncology · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Constitutive YAP activation resulting from dysregulated Hippo signaling drives tumor progression in mesothelioma and other cancers. VT3989, a first-in-class potent oral TEAD palmitoylation inhibitor, disrupts YAP transcriptional activity. Here we report the first-in-human phase 1/2 trial findings evaluating VT3989 in refractory solid tumors with a focus on mesothelioma. This study is ongoing, and we report results from the dose escalation and non-prespecified interim efficacy results of the expansion cohorts for which recruitment is ongoing. Dose escalation (n = 85) and expansion (n = 87) cohorts included 172 patients (135 mesothelioma). VT3989 exhibited a favorable safety profile with mostly grade 1-2 toxicities, including increased urine albumin:creatinine ratio (UACR), proteinuria, peripheral edema and fatigue. Proteinuria was reversible with dose adjustment and did not result in renal impairment. The overall response rate (ORR) was 26% in 47 patients with mesothelioma treated at clinically optimized doses, whereas the ORR was 32% (disease control rate 86%; median progression-free survival 10 months) in 22 patients with mesothelioma when clinically optimized doses and UACR thresholds were incorporated. These data provide the first early clinical proof of concept for effectively drugging the Hippo-YAP-TEAD pathway. VT3989 was recently awarded orphan drug designation and fast-track designation for the treatment of mesothelioma by the US Food and Drug Administration (FDA). ClinicalTrials.gov Identifier: NCT04665206 .
Indexed as
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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.