Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research
Rattachement africain : cn, us, hk. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are generally resistant to targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib, and there are no standard therapeutic options for advanced SDH-deficient GISTs. The precise oncogenic mechanisms of SDH mutations in GIST have not been elucidated. Olverembatinib, a novel multikinase inhibitor, has shown promising activity in treating imatinib-resistant GIST. We conducted a phase 1 study (NCT03594422) to evaluate the safety and antitumor activity of olverembatinib in 66 patients with unresectable/metastatic GIST/other solid tumors, including 26 with TKI-failed SDH-deficient GISTs. To our knowledge, this is the largest prospective clinical trial for this rare GIST subtype. The median follow-up was 14.5 (0.9-57.5) months. Olverembatinib was well tolerated; treatment-emergent adverse events (≥20%) included increases in hepatic transaminases, increases in leukocytes and neutrophils, anemia, and pyrexia. For SDH-deficient GISTs, confirmed partial responses were observed in 6 of the 26 evaluable patients (objective response rate, 23.1%; 95% CI, 9-43.7); an additional 16 (61.5%) did not progress during the first 6 months of treatment. This resulted in a clinical benefit rate of 84.6% (95% CI, 65.1-95.6), and the median progression-free survival was 25.7 months (95% CI, 12.9-NR). As a putative mechanism of action, translational research revealed significant lipid enrichment with the overexpression of lipid uptake-related genes and proteins, including CD36, fatty acid binding proteins, fatty acid transport proteins, and lipid metabolites, in SDH-deficient GIST patients, and olverembatinib suppressed lipid uptake and CD36 expression in GIST cells. Olverembatinib also exerts antitumor effects by inhibiting tumorigenic signaling pathways associated with hypoxia, angiogenesis, proliferation, and survival.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research
- Date Crossref
- 04/11/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Sun Yat-sen University Department of Gastric Surgery pays non établi dans la noticeUniversité ou école supérieure
-
Sun Yat-sen University Cancer Center pays non établi dans la noticeÉtablissement de santé
-
Ascentage Pharma Group Inc. (United States) pays non établi dans la noticeEntreprise
-
Shanghai Medical College of Fudan University Department of Oncology pays non établi dans la noticeUniversité ou école supérieure
-
Fudan University Shanghai Cancer Center Department of Gastric Surgery pays non établi dans la noticeÉtablissement de santé
-
Zhengzhou University Department of General Surgery pays non établi dans la noticeUniversité ou école supérieure
-
Henan Cancer Hospital pays non établi dans la noticeÉtablissement de santé
-
Union Hospital pays non établi dans la noticeÉtablissement de santé
-
Huazhong University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
-
Guangdong Academy of Medical Sciences pays non établi dans la noticeÉtablissement de santé
-
Guangdong Provincial People's Hospital Department of Gastrointestinal Surgery pays non établi dans la noticeÉtablissement de santé
-
People's Liberation Army No. 150 Hospital pays non établi dans la noticeÉtablissement de santé
Department of Gastric Surgery — Sun Yat-sen University, Sun Yat-sen University Cancer Center et Ascentage Pharma Group Inc. (United States), avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.