Trial reportCancer discovery2023
Clinical Activity and Exploratory Resistance Mechanism of Milademetan, an MDM2 Inhibitor, in Intimal Sarcoma with MDM2 Amplification: An Open-Label Phase Ib/II Study.
Trial report in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Milademetan in Advanced Solid Tumors with MDM2 Amplification and Wild-type TP53: Preclinical and Phase II Clinical Trial Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- TWIST1 bridges p53 and MDM2 and impairs the efficacy of MDM2 inhibitors.Journal of experimental & clinical cancer research : CR · 2026Article
- Evolving phase I oncology trials in the precision medicine era: design, outcomes, and geographic access.ESMO real world data and digital oncology · 2026Article
- Dual Left Atrial Masses Causing Inflow Obstruction: A Rare Presentation of Primary Cardiac Intimal Sarcoma.Vascular health and risk management · 2026Article
- Integrative genomic and immune landscape analysis of intimal sarcomas for emerging therapeutic targets and immunotherapy strategies.Frontiers in immunology · 2026Article
- Synergistic MDM2-STAT3 Inhibition Demonstrates Strong Anti-Leukemic Efficacy in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Article
- Brigimadlin (BI-907828) and napabucasin (BBI608) cooperatively trigger apoptosis in chronic lymphocytic leukemia cells by simultaneous iİnhibition of MDM2 and STAT3.Molecular biology reports · 2025Article
- Natural products that target p53 for cancer therapy.Journal of natural medicines · 2025Review
- Review
- Diagnosis and treatment of cardiac tumors.Medical oncology (Northwood, London, England) · 2025Review
- The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels.Nucleic acids research · 2025Article
- MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.NPJ precision oncology · 2025Article
- Targeting the MDM2-p53 Interaction with Siremadlin: A Promising Therapeutic Strategy for TreatingCancers · 2025Article
- Efficacy of anlotinib and chemotherapy combination as neoadjuvant therapy in the treatment of pulmonary artery intimal sarcoma: a case report.Frontiers in oncology · 2025Article
- Multi-omics analysis revealed potential use of immunotherapy and CDK4/6 inhibitors in intimal sarcoma.Frontiers in immunology · 2025Article
- Aortic intimal sarcoma with abdominal metastasis: case report and management approach.Frontiers in oncology · 2025Article
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Efficacy of surgery in the management of multiple recurrences of retroperitoneal dedifferentiated liposarcoma.World journal of surgical oncology · 2024Article
- Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers andJCO precision oncology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intimal sarcoma is an extremely rare, life-threatening malignant neoplasm. Murine double minute 2 (MDM2) amplification is observed in >70% of intimal sarcomas. Milademetan, an MDM2 inhibitor, may provide clinical benefit in this patient population. We conducted a phase Ib/II study in patients with MDM2-amplified, wild-type TP53 intimal sarcoma as a substudy of a large nationwide registry for rare cancers in Japan. Milademetan (260 mg) was administered orally once daily for 3 days every 14 days, twice in a 28-day cycle. Of 11 patients enrolled, 10 were included in the efficacy analysis. Two patients (20%) showed durable responses for >15 months. Antitumor activity correlated with TWIST1 amplification (P = 0.028) and negatively with CDKN2A loss (P = 0.071). Acquired TP53 mutations were detected in sequential liquid biopsies as a novel exploratory resistance mechanism to milademetan. These results suggest that milademetan could be a potential therapeutic strategy for intimal sarcoma. SIGNIFICANCE: Strategies to optimize outcomes could include the use of new biomarkers (TWIST1 amplification and CDKN2A loss) to select patients with MDM2-amplified intimal sarcoma who might benefit from milademetan and combination with other targeted treatments. Sequential liquid biopsy of TP53 can be used to evaluate disease status during treatment with milademetan. See related commentary by Italiano, p. 1765. This article is highlighted in the In This Issue feature, p. 1749.
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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.