ArticleInvestigational new drugs2021
Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors.
Article in Investigational new drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01462175 (A Multi-center, Open Label, First in Human Phase I Dose Escalation Study of Single Agent RO5503781, a Small Molecule MDM2 Antagonist, Administered Orally in Patients With Advanced Malignancies, Except Leukemia), which is not on this map. Cited by 23 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.
A Multi-center, Open Label, First in Human Phase I Dose Escalation Study of Single Agent RO5503781, a Small Molecule MDM2 Antagonist, Administered Orally in Patients With Advanced Malignancies, Except Leukemia
Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Brigimadlin versus Doxorubicin in Advanced Dedifferentiated Liposarcoma: Efficacy, Safety, and Translational Data from Brightline-1, a Randomized Phase II/III Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- 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
- A First-in-Human Phase I Study of Milademetan, an MDM2 Inhibitor, in Patients With Advanced Liposarcoma, Solid Tumors, or Lymphomas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1.International journal of molecular sciences · 2025Review
- Synergistic MDM2-STAT3 Inhibition Demonstrates Strong Anti-Leukemic Efficacy in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Article
- Article
- Review
- MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.NPJ precision oncology · 2025Article
- Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors.Frontiers in oncology · 2025Article
- CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.EClinicalMedicine · 2025Article
- Redefining Therapeutic Approaches in Colorectal Cancer: Targeting Molecular Pathways and Overcoming Resistance.International journal of molecular sciences · 2024Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Treatment options for biliary tract cancer: unmet needs, new targets and opportunities from both physicians' and patients' perspectives.Future oncology (London, England) · 2024Review
- Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.Frontiers in pharmacology · 2024Review
- The MDM2-p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study.Cancer discovery · 2023Article
- Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition.International journal of molecular sciences · 2023Article
- Review
- Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma.Frontiers in oncology · 2022Review
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
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Authors and funding
16 authors at 10 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aim The oral MDM2 antagonist idasanutlin inhibits the p53-MDM2 interaction, enabling p53 activation, tumor growth inhibition, and increased survival in xenograft models. Methods We conducted a Phase I study of idasanutlin (microprecipitate bulk powder formulation) to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, food effect, and clinical activity in patients with advanced malignancies. Schedules investigated were once weekly for 3 weeks (QW × 3), once daily for 3 days (QD × 3), or QD × 5 every 28 days. We also analyzed p53 activation and the anti-proliferative effects of idasanutlin. Results The dose-escalation phase included 85 patients (QW × 3, n = 36; QD × 3, n = 15; QD × 5, n = 34). Daily MTD was 3200 mg (QW × 3), 1000 mg (QD × 3), and 500 mg (QD × 5). Most common adverse events were diarrhea, nausea/vomiting, decreased appetite, and thrombocytopenia. Dose-limiting toxicities were nausea/vomiting and myelosuppression; myelosuppression was more frequent with QD dosing and associated with pharmacokinetic exposure. Idasanutlin exposure was approximately dose proportional at low doses, but less than dose proportional at > 600 mg. Although inter-patient variability in exposure was high with all regimens, cumulative idasanutlin exposure over the whole 28-day cycle was greatest with a QD × 5 regimen. No major food effect on pharmacokinetic exposure occurred. MIC-1 levels were higher with QD dosing, increasing in an exposure-dependent manner. Best response was stable disease in 30.6% of patients, prolonged (> 600 days) in 2 patients with sarcoma. Conclusions Idasanutlin demonstrated dose- and schedule-dependent p53 activation with durable disease stabilization in some patients. Based on these findings, the QD × 5 schedule was selected for further development.
trial registrationNCT01462175 (ClinicalTrials.gov), October 31, 2011.
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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.