ArticleBlood advances2019
Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 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
- Pharmacokinetics and Macrophage Inhibitory Cytokine-1 Pharmacodynamics of the Murine Double Minute 2 Inhibitor, Navtemadlin (KRT-232) in Fed and Fasted Healthy Subjects.Clinical pharmacology in drug development · 2022Trial
- Reciprocal compensation of caspase-2 and p53 regulates the DNA damage response in HCT116 colon cancer cells.The Journal of biological chemistry · 2026Article
- MDM2 inhibitors in myeloid cancers: from basic biology to clinical use in myeloproliferative neoplasms.Leukemia · 2026Review
- Exploiting cellular senescence in hematologic malignancies.Translational oncology · 2026Review
- p53: from understanding its structure to advances in therapeutic targeting.Signal transduction and targeted therapy · 2026Review
- Chemoradiation Reprograms Tumor Cells and the Immune Microenvironment in Cervical Cancer.Cancer research · 2026Article
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- 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
- Synergistic Activity of Combined FLT3-ITD and MDM2 Inhibition with Quizartinib and Milademetan in FLT3-ITD Mutant/TP53 Wild-type Acute Myeloid Leukemias.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- ZNF146 accelerates lung adenocarcinoma progression through MDM2/p53 and PHGDH/ferroptosis.Cell & bioscience · 2025Article
- Review
- A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma.Science translational medicine · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- An MDM2 degrader shows potent cytotoxicity to MDM2-overexpressing acute lymphoblastic leukemia cells with minimal toxicity to normal cells/tissues.Cancer letters · 2024Article
- Identification of RBM15 as a prognostic biomarker in prostate cancer involving the regulation of prognostic m6A-related lncRNAs.European journal of medical research · 2024Article
13 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
10 authors at 6 institutions in 1 country.
Funding
Abstract
This open-label, phase 1 study evaluated the safety, pharmacokinetics, and maximum tolerated dose of AMG 232, an investigational oral, selective mouse double minute 2 homolog inhibitor in relapsed/refractory acute myeloid leukemia (AML). AMG 232 was administered orally once daily for 7 days every 2 weeks (7 on/off) at 60, 120, 240, 360, 480, or 960 mg as monotherapy (arm 1) or at 60 mg with trametinib 2 mg (arm 2). Dose-limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics, clinical and pharmacodynamic response, and expression of p53 target genes were assessed. All 36 patients received AMG 232. No DLTs occurred in arm 1, and 360 mg was the highest test dose; dose escalation was halted due to gastrointestinal AEs at higher doses. One of ten patients in arm 2 had a DLT (grade 3 fatigue); 60 mg was the highest dose tested with trametinib. Common treatment-related AEs (any grade) included nausea (58%), diarrhea (56%), vomiting (33%), and decreased appetite (25%). AMG 232 exhibited linear pharmacokinetics unaffected by coadministration with trametinib. Serum macrophage inhibitor cytokine-1 and bone marrow expression of
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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.