2026-04-17T03:28:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/81592025-10-24T10:40:35Zcom_2072_378070com_2072_378040col_2072_378092

A multicenter, dose-finding, phase 1b study of imatinib in combination with alpelisib as third-line treatment in patients with advanced gastrointestinal stromal tumor Pantaleo, Maria Abbondanza Heinrich, Michael C. Valverde Morales, Claudia Maria Schöfski, Patrick Grignani, Giovanni Italiano, Antoine Aparell digestiu - Càncer - Tractament Avaluació de resultats (Assistència sanitària) DISEASES::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Digestive System Diseases::Gastrointestinal Stromal Tumors Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome ENFERMEDADES::enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::enfermedades del sistema digestivo::tumores del estroma gastrointestinal Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento Alpelisib; Gastrointestinal stromal tumor; Imatinib Alpelisib; Tumor estromal gastrointestinal; Imatinib Alpelisib; Tumor estromal gastrointestinal; Imatinib Background Acquired resistance to approved tyrosine kinase inhibitors limits their clinical use in patients with gastrointestinal stromal tumor (GIST). This study investigated the safety, tolerability and efficacy of alpelisib, a phosphatidylinositol 3-kinase inhibitor, used in combination with imatinib in patients with advanced GIST who had failed prior therapy with both imatinib and sunitinib. Methods This phase 1b, multicenter, open-label study consisted of 2 phases: dose escalation and dose expansion. Dose escalation involved 200 mg once daily (QD) alpelisib, initially, followed by 250 and 350 mg. These were combined with 400 mg QD imatinib until maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) of alpelisib in combination with imatinib was determined. This MTD/RP2D dose was tested to evaluate the clinical activity of this combination in dose expansion. Results Fifty-six patients were enrolled, 21 and 35 in the dose escalation and expansion phases, respectively. The MTD of alpelisib given with imatinib was determined as 350 mg QD. Combination treatment showed partial response in 1 (2.9%) and stable disease in 15 (42.9%) patients. Median progression-free survival was 2 months (95% CI 1.8–4.6). Overall, 92.9% patients had adverse events (AEs) while 46.4% had grade 3/4 AEs, hyperglycemia being the most common (23.2%). Conclusions The MTD of alpelisib was estimated as 350 mg QD when used in combination with imatinib 400 mg QD after oral administration in patients with advanced GIST. The safety and tolerability profile of this combination was acceptable; however, the combination did not demonstrate sufficient clinical activity to justify additional clinical testing. The study was funded by the Novartis Pharma AG, Basel, Switzerland. 2025-10-24T10:40:35Z 2025-10-24T10:40:35Z 2025-10-24T10:40:35Z 2022-09-12T10:10:45Z 2022-09-12T10:10:45Z 2022-05-06 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/8159 BMC Cancer;22 https://doi.org/10.1186/s12885-022-09610-4 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess BMC Scientia