dc.contributor.author | Elez, E | |
dc.contributor.author | Cubillo, A | |
dc.contributor.author | Alfonso, PG | |
dc.contributor.author | Middleton, MR | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Alkuzweny, B | |
dc.contributor.author | Alcasid, A | |
dc.contributor.author | Zhang, X | |
dc.contributor.author | Van Cutsem, E | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-07-03T12:27:46Z | |
dc.date.available | 2024-07-03T12:27:46Z | |
dc.date.issued | 2024-04-11 | |
dc.identifier | ARTN 446 | |
dc.identifier | 10.1186/s12885-024-12153-5 | |
dc.identifier.citation | BMC Cancer, 2024, 24 (1), pp. 446 - | en_US |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6274 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.doi | 10.1186/s12885-024-12153-5 | |
dc.identifier.doi | 10.1186/s12885-024-12153-5 | |
dc.description.abstract | BACKGROUND: In patients with previously treated RAS-mutated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), a multicenter open-label phase 1b/2 trial was conducted to define the safety and efficacy of the MEK1/MEK2 inhibitor binimetinib in combination with the immune checkpoint inhibitor (ICI) nivolumab (anti-PD-1) or nivolumab and another ICI, ipilimumab (anti-CTLA4). METHODS: In phase 1b, participants were randomly assigned to Arm 1A (binimetinib 45 mg twice daily [BID] plus nivolumab 480 mg once every 4 weeks [Q4W]) or Arm 1B (binimetinib 45 mg BID plus nivolumab 480 mg Q4W and ipilimumab 1 mg/kg once every 8 weeks [Q8W]) to determine the maximum tolerable dose (MTD) and recommended phase 2 dose (RP2D) of binimetinib. The MTD/RP2D was defined as the highest dosage combination that did not cause medically unacceptable dose-limiting toxicities in more than 35% of treated participants in Cycle 1. During phase 2, participants were randomly assigned to Arm 2A (binimetinib MTD/RP2D plus nivolumab) or Arm 2B (binimetinib MTD/RP2D plus nivolumab and ipilimumab) to assess the safety and clinical activity of these combinations. RESULTS: In phase 1b, 21 participants were randomized to Arm 1A or Arm 1B; during phase 2, 54 participants were randomized to Arm 2A or Arm 2B. The binimetinib MTD/RP2D was determined to be 45 mg BID. In phase 2, no participants receiving binimetinib plus nivolumab achieved a response. Of the 27 participants receiving binimetinib, nivolumab, and ipilimumab, the overall response rate was 7.4% (90% CI: 1.3, 21.5). Out of 75 participants overall, 74 (98.7%) reported treatment-related adverse events (AEs), of whom 17 (22.7%) reported treatment-related serious AEs. CONCLUSIONS: The RP2D binimetinib regimen had a safety profile similar to previous binimetinib studies or nivolumab and ipilimumab combination studies. There was a lack of clinical benefit with either drug combination. Therefore, these data do not support further development of binimetinib in combination with nivolumab or nivolumab and ipilimumab in RAS-mutated MSS mCRC. TRIAL REGISTRATION: NCT03271047 (09/01/2017). | |
dc.format | Electronic | |
dc.format.extent | 446 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | BMC | en_US |
dc.relation.ispartof | BMC Cancer | |
dc.rights.uri | https://creativecommons.org/publicdomain/zero/1.0/ | en_US |
dc.subject | Binimetinib | |
dc.subject | Colorectal cancer | |
dc.subject | Ipilimumab | |
dc.subject | MEK1 | |
dc.subject | MSS | |
dc.subject | Nivolumab | |
dc.subject | RAS | |
dc.subject | Humans | |
dc.subject | Nivolumab | |
dc.subject | Ipilimumab | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Mutation | |
dc.subject | Microsatellite Repeats | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Benzimidazoles | |
dc.title | Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-stable metastatic colorectal cancer with RAS mutations in an open-label phase 1b/2 study. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2024-03-20 | |
dc.date.updated | 2024-07-03T12:24:23Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1186/s12885-024-12153-5 | en_US |
rioxxterms.licenseref.startdate | 2024-04-11 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/38600471 | |
pubs.issue | 1 | |
pubs.organisational-group | ICR | |
pubs.organisational-group | ICR/Primary Group | |
pubs.organisational-group | ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1186/s12885-024-12153-5 | |
pubs.volume | 24 | |
dc.contributor.icrauthor | Chau, Ian | |
icr.provenance | Deposited by Mr Arek Surman on 2024-07-03. Deposit type is initial. No. of files: 1. Files: Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-sta.pdf | |