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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorYap, Timothy A.
dc.contributor.authorVieito Villar, Maria
dc.contributor.authorBaldini, Capucine
dc.contributor.authorSepúlveda, Juan Manuel
dc.contributor.authorKondo, Shunsuke
dc.contributor.authorSimonelli, Matteo
dc.date.accessioned2022-01-27T09:59:39Z
dc.date.available2022-01-27T09:59:39Z
dc.date.issued2021-12
dc.identifier.citationYap TA, Vieito M, Baldini C, Sepúlveda-Sánchez JM, Kondo S, Simonelli M, et al. First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer. Clin Cancer Res. 2021 Dec;27(24):6666–76.
dc.identifier.issn1557-3265
dc.identifier.urihttp://hdl.handle.net/11351/6913
dc.descriptionAdvanced Cancer; Transforming Growth Factor beta
dc.description.abstractPurpose: A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer. Patients and Methods: This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation). Results: Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel. Conclusions: LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.relation.ispartofseriesClinical Cancer Research;27(24)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectQuimioteràpia combinada
dc.subjectCàncer - Quimioteràpia - Complicacions
dc.subjectMedicaments - Efectes secundaris
dc.subject.meshNeoplasms
dc.subject.mesh/drug therapy
dc.subject.meshCombined Modality Therapy
dc.subject.mesh/adverse effects
dc.titleFirst-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1158/1078-0432.CCR-21-1504
dc.subject.decsneoplasias
dc.subject.decs/farmacoterapia
dc.subject.decstratamiento combinado
dc.subject.decs/efectos adversos
dc.relation.publishversionhttps://doi.org/10.1158/1078-0432.CCR-21-1504
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Yap TA] Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas. [Vieito M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Baldini C] Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France. [Sepúlveda-Sánchez JM] Hospital Universitario 12 de Octubre, Madrid, Spain. [Kondo S] National Cancer Center Hospital, Tokyo, Japan. [Simonelli M] Department of Biomedical Sciences, Humanitas University, Milan, Italy. IRCCS Humanitas Cancer Center, Humanitas Research Hospital, Milan, Italy
dc.identifier.pmid34548321
dc.identifier.wos000732481500001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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