ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis.Blood advances · 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
- Genomic landscape and tumor immune microenvironment of osteosarcoma: Bridging mechanistic insights to precision therapeutics.Bone reports · 2026Review
- Phenotypic screening for small molecules that lower PrP in cultured cells.Molecular and cellular neurosciences · 2026Article
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- p53 mutation-associated prognosis across cancer types underlines hematological malignancy as an applicable cancer type to p53-rescue therapy.Fundamental research · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Article
- Phenotypic screening for small molecules that lower PrP in cultured cells.bioRxiv : the preprint server for biology · 2026Article
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Population PK/PD Modeling for Evaluation of Intertwining Effects of Drug and Disease on Thrombocytopenia in Acute Leukemias.CPT: pharmacometrics & systems pharmacology · 2026Article
- Mutant Isocitrate Dehydrogenase 1 Sensitizes Intrahepatic Cholangiocarcinoma Cells to MDM2 Inhibitors.Cancer research communications · 2026Article
- Research Progress on Small Molecule Inhibitors of MDM2-p53 Protein-protein Interaction.Anti-cancer agents in medicinal chemistry · 2026Review
- Unraveling the molecular landscape of pancreatic cancer: a systems biology approach to identify therapeutic targets.Discover oncology · 2025Article
- Article
- MDM2 in Tumor Biology and Cancer Therapy: A Review of Current Clinical Trials.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
- 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
- Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML.Journal of hematology & oncology · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 19 institutions in 11 countries.
Funding
Abstract
purposeThis phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53-MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. PATIENTS AND
methodsInitial dosing regimens were: 1A (day 1; 21-day cycle; dose 12.5-350 mg) and 2A (days 1-14; 28-day cycle; dose 1-20 mg). Alternative regimens included 1B (days 1 and 8; 28-day cycle) and 2C (days 1-7; 28-day cycle). The primary endpoint was incidence of dose-limiting toxicities (DLT) during cycle 1.
resultsOverall, 115 patients with solid tumors and 93 with hematologic malignancies received treatment. DLTs occurred in 8/92 patients with solid tumors and 10/53 patients with hematologic malignancies. In solid tumors, an RDE of 120 mg was defined in 1B. In hematologic tumors, RDEs were defined in 1A: 250 mg, 1B: 120 mg, and 2C: 45 mg. More patients with hematologic malignancies compared with solid tumors experienced grade 3/4 treatment-related adverse events (71% vs. 45%), most commonly resulting from myelosuppression. These were more frequent and severe in patients with hematologic malignancies; 22 patients exhibited tumor lysis syndrome. Overall response rates at the RDEs were 10.3% [95% confidence interval (CI), 2.2-27.4] in solid tumors and 4.2% (95% CI, 0.1-21.1), 20% (95% CI, 4.3-48.1), and 22.2% (95% CI, 8.6-42.3) in acute myeloid leukemia (AML) in 1B, 1A, and 2C, respectively.
conclusionsA common safety profile was identified and preliminary activity was noted, particularly in AML. Comprehensive investigation of dosing regimens yielded recommended doses/regimens for future combination studies.
Indexed as
Identifiers
What OpenQuestion holds
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.