Evidence map›Paper›PMID 33211315›Full record

ArticleTargeted oncology2021

Selective Oral MEK1/2 Inhibitor Pimasertib in Metastatic Melanoma: Antitumor Activity in a Phase I, Dose-Escalation Trial.

Céleste Lebbé, Antoine Italiano, Nadine Houédé, Ahmad Awada, Philippe Aftimos, Thierry Lesimple, Monica Dinulescu, Jan H M Schellens, Suzanne Leijen, Sylvie Rottey and 10 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

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 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 28% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT00982865 phase1completednot on this map

A Multicenter, Open Label, Phase I Trial of the MEK Inhibitor MSC1936369B Given Orally to Subjects With Solid Tumours

TypeinterventionalSponsorMerck KGaA, Darmstadt, GermanyRan2007 to 2016Enrolled182ConditionsSolid Tumors, CancerArmsMSC1936369B
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 13 institutions in 8 countries.

Céleste LebbéDermatology and CIC, AP-HP, Saint Louis Hospital, and Université de Paris, INSERM U976, Paris, France. celeste.lebbe@aphp.fr.
Antoine ItalianoEarly Phase Trials and Sarcoma Units, Institut Bergonié, Bordeaux, France.
Nadine HouédéMedical Oncology, Institut de Cancérologie du Gard, CHU Caremeau, Nîmes, France.
Ahmad AwadaOncology Médicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Philippe AftimosOncology Médicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
Thierry LesimpleMedical Oncology Department, Comprehensive Cancer Center Eugène Marquis, Rennes, France.
Monica DinulescuDepartment of Dermatology, Rennes University Hospital, Rennes, France.
Jan H M SchellensDivision of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Suzanne LeijenDivision of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Sylvie RotteyDepartment of Medical Oncology, Ghent University Hospital and Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Vibeke KruseDepartment of Medical Oncology, Ghent University Hospital and Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Richard KeffordCrown Princess Mary Cancer Centre Westmead Hospital, Faculty of Medicine and Health Sciences, Macquarie University, and Melanoma Institute Australia, Sydney, NSW, Australia.
Eric RaymondMedical Oncology, Groupe Hospitalier Paris St Joseph, Paris, France.
Sandrine FaivreMedical Oncology, Beaujon University Hospital, Clichy, France.
Celine PagesDermatology and CIC, AP-HP, Saint Louis Hospital, and Université de Paris, INSERM U976, Paris, France.
Carlos Gomez-RocaClinical Research Unit, Institut Universitaire du Cancer, Oncopole, Toulouse, France.
Armin SchuelerGlobal Biostatistics and Epidemiology, EMD Serono Research and Development Institute, Inc. (an affiliate of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA.
Samantha GoodstalTranslational Research, EMD Serono Research and Development Institute, Inc. (an affiliate of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA.
Giorgio MassiminiEarly Clinical Oncology Global Clinical Development Biopharma, Merck KGaA, Darmstadt, Germany.
Jean-Pierre DelordClinical Research Unit, Institut Universitaire du Cancer, Oncopole, Toulouse, France.
Merck (Germany) · DEGhent University Hospital · BEInserm · FRInstitut universitaire du cancer de Toulouse Oncopole · FRThe Netherlands Cancer Institute · NLUniversité Libre de Bruxelles · BECentre Eugène Marquis · FRCentre Hospitalier Universitaire de Rennes · FRHôpital Beaujon · FRHôpital Saint Joseph · FRInstitut de Cancérologie de Bourgogne · FRUniversité de Bordeaux · FRWestmead Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPimasertib is a selective, potent mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor.

objectivesThe aim of this study was to describe the efficacy, safety, and pharmacodynamics of pimasertib at pharmacologically active doses in a cohort of patients with locally advanced/metastatic melanoma from a first-in-human study of pimasertib.

methodsThis was a phase I, open-label, two-part, dose-escalation study. Part 1 was conducted in patients with solid tumors and identified the maximum tolerated dose, while Part 2 was restricted to patients with advanced/metastatic melanoma. Endpoints included safety, pharmacodynamics, and antitumor activity. We present data for patients with melanoma only from both parts of the study.

resultsIn total, 93 patients with melanoma received pimasertib, 89 of whom received pharmacologically active doses (28-255 mg/day) across four dose regimens in the two parts of the study. The objective response rate was 12.4% (11/89): complete response (n = 1) and partial response (PR; n = 10). Six patients responded for > 24 weeks. Nine of the 11 responders had tumors with B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF; n = 6) and/or NRAS Proto-Oncogene, GTPase (NRAS; n = 3) mutations. Forty-six patients had stable disease (SD). In patients with ocular melanoma (n = 13), best overall response was PR (n = 1), SD (n = 11), and disease progression (n = 1). Phosphorylated extracellular signal-regulated kinase (pERK) levels were substantially reduced within 2 h of treatment and inhibition was sustained with continuous twice-daily dosing. Treatment-related, recurrent, grade 3 or higher adverse events were reported in eight patients, including diarrhea, and skin and ocular events.

conclusionResults from this phase I study indicate that pimasertib has clinical activity in patients with locally advanced/metastatic melanoma, particularly BRAF- and NRAS-mutated tumors, at clinically relevant doses associated with pERK inhibition in peripheral blood mononuclear cells.

trial registrationClinicalTrials.gov, NCT00982865.

Indexed as

AdultAgedAged, 80 and overFemaleHumansMaleMelanomaMiddle AgedNiacinamideProtein Kinase InhibitorsProto-Oncogene MasMAS1 protein, humanN-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamideNiacinamideProtein Kinase InhibitorsProto-Oncogene Mas

Identifiers

PMID33211315
OpenAlexW3105227288

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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.