Evidence map›Paper›PMID 41484121›Full record

Trial reportNature communications2026

Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial.

April A N Rose, Jennifer Maxwell, Emmanuelle Rousselle, Chantel L Mukonoweshuro, Islam E Elkholi, Melody Riaud, Marco Biondini, Erica Cianfarano, Isabel Soria-Bretones, Chantal Tobin and 19 more

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03839342 (Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

NCT03839342 phase2active not recruitingnot on this map

Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations

TypeinterventionalSponsorUniversity Health Network, TorontoRan2019 to 2026Enrolled26ConditionsSolid TumorArmsBinimetinib, Encorafenib
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

29 authors.

April A N Rose *Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. april.rose@mcgill.ca.ORCID http://orcid.org/0000-0002-9845-4603
Jennifer Maxwell *Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0009-0000-3433-6520
Emmanuelle Rousselle *Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0009-0006-8831-7871
Chantel L MukonoweshuroLady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.ORCID http://orcid.org/0009-0007-7425-8345
Islam E ElkholiGerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-8019-2481
Melody RiaudGerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
Marco BiondiniGoodman Cancer Institute, McGill University, Montreal, QC, Canada.
Erica CianfaranoMontreal Neurological Institute, McGill University, Montreal, QC, Canada.
Isabel Soria-BretonesGerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada.
Chantal TobinPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Meghan McGuirePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Rhoda W Y LawPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Andrew J EliaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Ben X WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Ian KingDivision of Clinical Laboratory Genetics, University Health Network, Toronto, ON, Canada.
Tong ZhangDivision of Clinical Laboratory Genetics, University Health Network, Toronto, ON, Canada.
Trevor J PughPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Zaid Saeed KamilPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Marcus ButlerPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-9840-7057
Frances A ShepherdPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Natasha B LeighlPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-3249-4602
Albiruni Abdul RazakPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Aaron HansenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-2363-8707
Samuel D SaibilPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Philippe L BedardPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-6771-2999
Peter M SiegelDivision of Experimental Medicine, McGill University, Montreal, QC, Canada.ORCID http://orcid.org/0000-0002-5568-6586
Lillian L SiuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-3500-0540
David W CesconPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-1080-0998
Anna SpreaficoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. anna.spreafico@uhn.ca.ORCID http://orcid.org/0000-0002-3034-3042

Funding

Canada Foundation for Innovation (Fondation canadienne pour l'innovation) 42153Conquer Cancer Foundation (Conquer Cancer Foundation of the American Society of Clinical Oncology) 707457Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 180379Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 197819
6 · The paper itself

Abstract

Class 2 and 3 non-V600E BRAF mutations are oncogenic drivers in many cancer types. Currently, there are no established targeted therapies with proven efficacy for cancers with non-V600E BRAF mutations. We developed the investigator-initiated, Phase II BEAVER clinical trial (NCT03839342) to evaluate the efficacy of BRAF and MEK inhibitors in patients with non-V600E BRAF mutations. The primary outcome was objective response rate (ORR). The best ORR was 14% (3/21), the primary endpoint was not met. By analyzing genomic data from patient tumors, circulating tumor DNA (ctDNA), patient-derived xenograft (PDX) models generated from enrolled patients, and Class 2 & 3 BRAF mutant cell lines, we discovered MAPK-dependent and independent mechanisms of resistance to BRAF/MEK inhibition. These mechanisms include the acquisition of new mutations in NRAS, MAP2K1, RAF1, and RB in ctDNA at the time of disease progression. CDK4/6 and SHP2 emerge as mediators of intrinsic resistance to BRAF/MEK inhibition in Class 2 & 3 BRAF mutant tumors. Therapeutic strategies combining CDK4/6 or SHP2 inhibitors with BRAF/MEK inhibitors in preclinical models show greater efficacy than BRAF/MEK inhibitors alone in these cancers.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBenzimidazolesCarbamatesNeoplasmsProto-Oncogene Proteins B-rafSulfonamidesAdultAgedAnimalsCell Line, TumorCirculating Tumor DNADrug Resistance, NeoplasmFemaleHumansMaleMAP Kinase Kinase 1BenzimidazolesbinimetinibBRAF protein, humanCarbamatesCirculating Tumor DNAencorafenibMAP Kinase Kinase 1Protein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamides

Identifiers

PMID41484121
PMCPMC12873207

What OpenQuestion holds

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Read underepoch 390

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.