{"doi":"10.1093/oncolo/oyad210","title":"Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type <i>RAS</i> Metastatic Colorectal Cancer","abstract":"INTRODUCTION: Activating RAS gene mutations occur in approximately 55% of patients with metastatic colorectal cancer (mCRC) and are associated with poorer clinical outcomes due to epidermal growth factor receptor (EGFR) blockade resistance. Combined EGFR and mitogen-activated protein kinase (MEK) inhibition may extend response to EGFR inhibition and overcome acquired resistance. This phase Ib/II dose escalation trial evaluated the safety and activity of dual inhibition with binimetinib (MEK1/2 inhibitor) and panitumumab (EGFR inhibitor [EGFRi]) in patients with RAS mutant or BRAF wild type (WT)/RAS WT mCRC. METHODS: Phase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and RAS mutational status. RESULTS: No patients in the phase Ib portion (n = 10) had a response; 70% of patients had stable disease. In the phase II portion (n = 43), overall response rate (ORR, confirmed) was 2.3% with one partial response in the RAS WT group, DCR was 30.2%, and median progression-free survival was 1.8 months (95%CI, 1.6-3.3). All patients experienced ≥1 adverse event, with the most common being diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%). Most patients required treatment interruption or dose reduction due to difficulties tolerating treatment. CONCLUSIONS: The combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT RAS mCRC, independent of EGFRi treatment history (Trial registration: NCT01927341).","journal":"The Oncologist","year":2023,"id":382333,"datarank":0.250349622463412,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.04240546829542842,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.04240546829542842,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01927341"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":90752,"name":"Rona Yaeger","orcid":"0000-0002-7233-5454","position":1,"is_corresponding":false},{"id":318655,"name":"Jean‐Pierre Delord","orcid":"0000-0001-7305-5561","position":2,"is_corresponding":false},{"id":35283,"name":"Josep Tabernero","orcid":"0000-0002-2495-8139","position":3,"is_corresponding":false},{"id":318654,"name":"Lillian L. Siu","orcid":"0000-0002-3500-0540","position":4,"is_corresponding":false},{"id":54191,"name":"Michel Ducreux","orcid":"0000-0001-8649-7449","position":5,"is_corresponding":false},{"id":91851,"name":"Salvatore Siena","orcid":"0000-0002-2681-2846","position":6,"is_corresponding":false},{"id":91850,"name":"Élena Elez","orcid":"0000-0002-4653-6324","position":7,"is_corresponding":false},{"id":1148512,"name":"Stefan Kasper","orcid":"0000-0002-5947-8733","position":8,"is_corresponding":false},{"id":84395,"name":"Thomas Zander","orcid":"0000-0002-4266-6818","position":9,"is_corresponding":false},{"id":91856,"name":"Neeltje Steeghs","orcid":"0000-0003-2989-2279","position":10,"is_corresponding":false},{"id":1029421,"name":"Danielle Murphy","orcid":"0000-0001-6894-9173","position":11,"is_corresponding":false},{"id":83217,"name":"Michelle Edwards","orcid":null,"position":12,"is_corresponding":false},{"id":226651,"name":"Zev A. Wainberg","orcid":"0000-0002-7142-1246","position":13,"is_corresponding":false},{"id":88015,"name":"Eric Van Cutsem","orcid":"0000-0002-6372-1230","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T01:17:17.113710Z","pmid":"37597246","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}