ArticleBritish journal of cancer2019
A phase I study of the HDM2 antagonist SAR405838 combined with the MEK inhibitor pimasertib in patients with advanced solid tumours.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01985191 (A Phase 1 Study of Combination Therapy With SAR405838 and Pimasertib in Patients With Advanced Cancer), which is not on this map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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 Phase 1 Study of Combination Therapy With SAR405838 and Pimasertib in Patients With Advanced Cancer
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Spirooxindole Derivatives as Emerging Scaffolds in Drug Discovery: Synthetic Strategies, Structure-Activity Relationship, and Biological Activities.ChemMedChem · 2026Review
- Reciprocal compensation of caspase-2 and p53 regulates the DNA damage response in HCT116 colon cancer cells.The Journal of biological chemistry · 2026Article
- Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.Epigenomics · 2025Review
- The Therapeutic Potential of Spirooxindoles in Cancer: A Focus on p53-MDM2 Modulation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Insights into the Interaction Mechanisms of Peptide and Non-Peptide Inhibitors with MDM2 Using Gaussian-Accelerated Molecular Dynamics Simulations and Deep Learning.Molecules (Basel, Switzerland) · 2024Article
- Targeting Hdm2 and Hdm4 in Anticancer Drug Discovery: Implications for Checkpoint Inhibitor Immunotherapy.Cells · 2024Review
- Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Differentially expressed platelet activation-related genes in dogs with stage B2 myxomatous mitral valve disease.BMC veterinary research · 2023Article
- Combination Therapy With MDM2 and MEK Inhibitors Is Effective in Patient-Derived Models of Lung Adenocarcinoma With Concurrent Oncogenic Drivers and MDM2 Amplification.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Article
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy.International journal of molecular sciences · 2023Review
- Raman Spectroscopy Characterization of Multi-Functionalized Liposomes as Drug-Delivery Systems for Neurological Disorders.Nanomaterials (Basel, Switzerland) · 2023Article
- Discovery of Nanomolar-Affinity Pharmacological Chaperones Stabilizing the Oncogenic p53 Mutant Y220C.ACS pharmacology & translational science · 2022Article
- Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials.Journal of hematology & oncology · 2022Review
- Dispirooxindole-β-Lactams: Synthesis via Staudinger Ketene-Imine Cycloaddition and Biological Evaluation.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThis phase I, open-label, dose-escalation study evaluated the safety, pharmacokinetics and pharmacodynamics of combination therapy with the HDM2 inhibitor SAR405838 and the MEK1/2 inhibitor pimasertib administered orally once daily (QD) or twice daily (BID) in locally advanced or metastatic solid tumours (NCT01985191).
methodsPatients with locally advanced or metastatic solid tumours with documented wild-type TP53 and RAS or RAF mutations were enroled. A 3 + 3 dose-escalation design was employed. The primary objective was to assess maximum tolerated dose (MTD).
resultsTwenty-six patients were treated with SAR405838 200 or 300 mg QD plus pimasertib 60 mg QD or 45 mg BID. The MTD was SAR405838 200 mg QD plus pimasertib 45 mg BID. The most common dose-limiting toxicity was thrombocytopenia. The most frequently occurring treatment-related adverse events were diarrhoea (81%), increased blood creatine phosphokinase (77%), nausea (62%) and vomiting (62%). No significant drug-drug interactions were observed. The biomarkers MIC-1 and pERK were, respectively, upregulated and downregulated in response to study treatment. In 24 efficacy-evaluable patients, one patient (4%) had a partial response and 63% had stable disease.
conclusionsThe safety profile of SAR405838 and pimasertib combined was consistent with the safety profiles of both drugs. Preliminary antitumour activity was observed.
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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.