ArticleTargeted oncology2021
Selective Oral MEK1/2 Inhibitor Pimasertib: A Phase I Trial in Patients with Advanced Solid Tumors.
Article in Targeted oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00982865 (A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours), which is not on this map. Cited by 6 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 Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours
Who cites it
6 citing papers in PubMed, 10 citations in OpenAlex.
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Mucocutaneous toxicities from MEK inhibitors: a scoping review of the literature.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Review
- Raman Spectroscopy Characterization of Multi-Functionalized Liposomes as Drug-Delivery Systems for Neurological Disorders.Nanomaterials (Basel, Switzerland) · 2023Article
- Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival.International journal of molecular sciences · 2022Article
- Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.Targeted oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 13 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (Ras/Raf/MEK/ERK) signaling cascade is frequently constitutively activated in human cancers. Pimasertib is a selective and potent adenosine triphosphate non-competitive MEK1/2 inhibitor.
objectiveOur objectives were to describe the results of a phase I, first-in-human, dose-escalation trial of pimasertib that investigated the maximum tolerated dose, recommended phase II dose, and safety, as well as other endpoints. PATIENTS AND
methodsFour dosing schedules of pimasertib (once daily [qd], 5 days on, 2 days off; qd, 15 days on, 6 days off; continuous qd; continuous twice daily [bid]) were evaluated in patients with advanced solid tumors. Each treatment cycle lasted 21 days. The primary objective was to determine the maximum tolerated dose based on dose-limiting toxicities (DLTs) evaluated during cycle 1, and the recommended phase II dose (RP2D). Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and antitumor activity.
resultsOverall, 180 patients received pimasertib (dose range 1-255 mg/day). DLTs were mainly observed at doses ≥ 120 mg/day and included skin rash/acneiform dermatitis and ocular events, such as serous retinal detachment. The most common drug-related adverse events were consistent with class effects, including diarrhea, skin disorders, ocular disorders, asthenia/fatigue, and peripheral edema. The median time to maximum pimasertib concentration was 1.5 h across dosing schedules, and the apparent terminal half-life was 5 h across qd dosing schedules. Pimasertib decreased ERK phosphorylation within 2 h of administration, which was maintained for up to 8 h at higher doses and prolonged with bid dosing.
conclusionsBased on the safety profile and efficacy signals, a continuous bid regimen was the preferred dosing schedule and the RP2D was defined as 60 mg bid.
trial registrationClinicalTrials.gov, NCT00982865.
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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.