In EDS ansehen

The INSIGHT study: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11+17/18 mutations

Gespeichert in:
Bibliographische Detailangaben
Titel: The INSIGHT study: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations: a randomized, Phase III study of ripretinib versus sunitinib for advanced gastrointestinal stromal tumor with KIT exon 11+17/18 mutations
Autoren: Suzanne George, Jean-Yves Blay, Ping Chi, Robin L Jones, César Serrano, Neeta Somaiah, Hans Gelderblom, John R Zalcberg, William Reichmann, Kam Sprott, Paulina Cox, Matthew L Sherman, Rodrigo Ruiz-Soto, Michael C Heinrich, Sebastian Bauer
Weitere Verfasser: Institut Català de la Salut, [George S] Dana-Farber Cancer Institute, Boston, MA, USA. [Blay JY] Centre Léon Bérard, Lyon, France. [Chi P] Memorial Sloan Kettering Cancer Center, New York, NY, USA. Weill Cornell Medicine, New York, NY, USA. [Jones RL] Sarcoma Unit, The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Somaiah N] The University of Texas MD Anderson Cancer Center, Houston, TX, USA, Vall d'Hebron Barcelona Hospital Campus
Quelle: Future Oncol
Scientia
Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname
Verlagsinformationen: Informa UK Limited, 2024.
Publikationsjahr: 2024
Schlagwörter: Adult, Male, CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors, Clinical Trial Protocol, ctDNA mutational analysis, Other subheadings::Other subheadings::/therapeutic use, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, Gastrointestinal Stromal Tumors, sunitinib, Medizin, COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas, Otros calificadores::Otros calificadores::/uso terapéutico, INSIGHT, Antineoplastic Agents, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Connective Tissue::Gastrointestinal Stromal Tumors, gastrointestinal stromal tumor, tyrosine kinase inhibitor, Tracte gastrointestinal - Càncer - Tractament, ripretinib, Sunitinib, Humans, Urea, Protein Kinase Inhibitors, Aged, Gastrointestinal Neoplasms, Randomized Controlled Trials as Topic, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación, Other subheadings::Other subheadings::Other subheadings::/drug therapy, Exons, KIT mutations, Middle Aged, targeted therapy, Proto-Oncogene Proteins c-kit, Anomalies cromosòmiques, Treatment Outcome, Clinical Trials, Phase III as Topic, Drug Resistance, Neoplasm, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation, Mutation, Female, Phase III trial, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido conjuntivo::tumores del estroma gastrointestinal, predictive marker, Proteïnes quinases - Inhibidors - Ús terapèutic
Beschreibung: Somatic KIT activating mutations drive most gastrointestinal stromal tumors (GISTs). Disease progression eventually develops with first-line imatinib, commonly due to KIT secondary mutations, and different kinase inhibitors have various levels of treatment efficacy dependent on specific acquired resistance mutations. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor for patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib. Exploratory baseline circulating tumor DNA analysis from the second-line INTRIGUE trial determined that patients with advanced GIST previously treated with imatinib harboring primary KIT exon 11 mutations and secondary resistance mutations restricted to KIT exons 17/18 had greater clinical benefit with ripretinib versus sunitinib. We describe the rationale and design of INSIGHT (NCT05734105), an ongoing Phase III open-label study of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib exclusively harboring KIT exon 11 + 17/18 mutations detected by circulating tumor DNA. Clinical Trial Registration:NCT05734105 (ClinicalTrials.gov) Gastrointestinal stromal tumor (GIST) is rare, but it is the most common mesenchymal tumor (a type of tumor that develops from cells which give rise to soft tissues) of the gastrointestinal tract. The primary treatment for advanced GIST is medication that targets the abnormal mechanisms in cancer cells in order to block tumor growth and spread. Ripretinib is an inhibitor of a protein known as KIT, which is a member of the tyrosine kinase protein family and is involved in the growth of GIST. In a Phase III clinical trial called INTRIGUE, the effects of ripretinib and another receptor tyrosine kinase inhibitor, sunitinib, were compared in patients with advanced GIST previously treated with the drug imatinib. An exploratory analysis from the INTRIGUE trial that characterized baseline circulating tumor DNA in the blood showed a greater clinical benefit with ripretinib versus sunitinib in patients with gene mutations solely occurring in KIT exon 11 + 17 and/or 18 (exon 11 + 17/18). This article describes the rationale and design for a Phase III clinical trial called INSIGHT that will evaluate the benefit of ripretinib compared with sunitinib in patients with advanced GIST whose tumors have mutations in KIT exon 11 and KIT exon 17 and/or 18. Patients will receive ripretinib or sunitinib in 6-week cycles, and investigators will assess survival without cancer progression as the primary outcome, and overall survival, and response of the tumor to these two drugs as secondary outcomes. This article describes the rationale and design for the INSIGHT Phase III trial evaluating patients with second-line advanced GIST who harbor primary KIT exon 11 mutations and secondary resistance mutations restricted to the activation loop (KIT exons 17/18). Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal sarcoma, with approximately 80% of cases driven by activating mutations in KIT. Sunitinib is a multitargeted tyrosine kinase inhibitor (TKI) approved as a second-line therapy for advanced GIST after disease progression on or intolerance to imatinib. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA TKI approved as a fourth-line therapy for advanced GIST. Exploratory baseline circulating tumor DNA (ctDNA) analysis from INTRIGUE determined that patients with KIT exon 11 + 13/14 mutations had improved progression-free survival (PFS) and objective response rate (ORR) with sunitinib versus ripretinib, while those with KIT exon 11 + 17/18 mutations had improved PFS, ORR and overall survival (OS) and a better safety profile with ripretinib versus sunitinib. INSIGHT is an international, Phase III, randomized, multicenter, open-label study evaluating the efficacy of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib and who have KIT exon 11 mutations and co-occurring mutations exclusively in KIT exons 17/18, as identified by ctDNA. Approximately 54 patients will be randomized 2:1 to receive ripretinib 150 mg once daily (QD; continuous) or sunitinib 50 mg QD (4 weeks on/2 weeks off) in 6-week cycles. Eligible patients must have a histologic diagnosis of advanced GIST and co-occurring KIT exon 11 + 17/18 mutations confirmed by central laboratory ctDNA analysis, as well as radiologic progression on imatinib. The primary outcome measure is PFS based on blinded independent radiologic review (IRR) using modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1), while key secondary outcome measures are ORR based on blinded IRR using mRECIST v1.1 and OS. A PDF version of this infographic is available as supplemental material.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1744-8301
1479-6694
DOI: 10.1080/14796694.2024.2376521
DOI: 10.6084/m9.figshare.27110148
DOI: 10.6084/m9.figshare.27110148.v1
DOI: 10.6084/m9.figshare.27110148.v2
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/39229786
https://hdl.handle.net/11351/12128
https://hdl.handle.net/1887/4195712
https://www.ncbi.nlm.nih.gov/pubmed/39229786
https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&origin=inward&scp=85203297665
https://doi.org/10.1080/14796694.2024.2376521
Rights: CC BY NC ND
CC BY
URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
Dokumentencode: edsair.doi.dedup.....5a62c5d89635219ae27c0127fb1bfa60
Datenbank: OpenAIRE
Beschreibung
Abstract:Somatic KIT activating mutations drive most gastrointestinal stromal tumors (GISTs). Disease progression eventually develops with first-line imatinib, commonly due to KIT secondary mutations, and different kinase inhibitors have various levels of treatment efficacy dependent on specific acquired resistance mutations. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor for patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib. Exploratory baseline circulating tumor DNA analysis from the second-line INTRIGUE trial determined that patients with advanced GIST previously treated with imatinib harboring primary KIT exon 11 mutations and secondary resistance mutations restricted to KIT exons 17/18 had greater clinical benefit with ripretinib versus sunitinib. We describe the rationale and design of INSIGHT (NCT05734105), an ongoing Phase III open-label study of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib exclusively harboring KIT exon 11 + 17/18 mutations detected by circulating tumor DNA. Clinical Trial Registration:NCT05734105 (ClinicalTrials.gov) Gastrointestinal stromal tumor (GIST) is rare, but it is the most common mesenchymal tumor (a type of tumor that develops from cells which give rise to soft tissues) of the gastrointestinal tract. The primary treatment for advanced GIST is medication that targets the abnormal mechanisms in cancer cells in order to block tumor growth and spread. Ripretinib is an inhibitor of a protein known as KIT, which is a member of the tyrosine kinase protein family and is involved in the growth of GIST. In a Phase III clinical trial called INTRIGUE, the effects of ripretinib and another receptor tyrosine kinase inhibitor, sunitinib, were compared in patients with advanced GIST previously treated with the drug imatinib. An exploratory analysis from the INTRIGUE trial that characterized baseline circulating tumor DNA in the blood showed a greater clinical benefit with ripretinib versus sunitinib in patients with gene mutations solely occurring in KIT exon 11 + 17 and/or 18 (exon 11 + 17/18). This article describes the rationale and design for a Phase III clinical trial called INSIGHT that will evaluate the benefit of ripretinib compared with sunitinib in patients with advanced GIST whose tumors have mutations in KIT exon 11 and KIT exon 17 and/or 18. Patients will receive ripretinib or sunitinib in 6-week cycles, and investigators will assess survival without cancer progression as the primary outcome, and overall survival, and response of the tumor to these two drugs as secondary outcomes. This article describes the rationale and design for the INSIGHT Phase III trial evaluating patients with second-line advanced GIST who harbor primary KIT exon 11 mutations and secondary resistance mutations restricted to the activation loop (KIT exons 17/18). Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal sarcoma, with approximately 80% of cases driven by activating mutations in KIT. Sunitinib is a multitargeted tyrosine kinase inhibitor (TKI) approved as a second-line therapy for advanced GIST after disease progression on or intolerance to imatinib. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA TKI approved as a fourth-line therapy for advanced GIST. Exploratory baseline circulating tumor DNA (ctDNA) analysis from INTRIGUE determined that patients with KIT exon 11 + 13/14 mutations had improved progression-free survival (PFS) and objective response rate (ORR) with sunitinib versus ripretinib, while those with KIT exon 11 + 17/18 mutations had improved PFS, ORR and overall survival (OS) and a better safety profile with ripretinib versus sunitinib. INSIGHT is an international, Phase III, randomized, multicenter, open-label study evaluating the efficacy of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib and who have KIT exon 11 mutations and co-occurring mutations exclusively in KIT exons 17/18, as identified by ctDNA. Approximately 54 patients will be randomized 2:1 to receive ripretinib 150 mg once daily (QD; continuous) or sunitinib 50 mg QD (4 weeks on/2 weeks off) in 6-week cycles. Eligible patients must have a histologic diagnosis of advanced GIST and co-occurring KIT exon 11 + 17/18 mutations confirmed by central laboratory ctDNA analysis, as well as radiologic progression on imatinib. The primary outcome measure is PFS based on blinded independent radiologic review (IRR) using modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1), while key secondary outcome measures are ORR based on blinded IRR using mRECIST v1.1 and OS. A PDF version of this infographic is available as supplemental material.
ISSN:17448301
14796694
DOI:10.1080/14796694.2024.2376521