Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial

DeAngelo, Daniel J.; Radia, Deepti H.; George, Tracy I.; Robinson, William A.; Quiery, Albert T.; Drummond, Mark W.; Bose, Prithviraj; Hexner, Elizabeth O.; Winton, Elliott F.; Horny, Hans-Peter; Tugnait, Meera; Schmidt-Kittler, Oleg; Evans, Erica K.; Lin, Hui-Min; Mar, Brenton G.; Verstovsek, Srdan; Deininger, Michael W. und Gotlib, Jason (2021): Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. In: Nature Medicine, Bd. 27, Nr. 12: S. 2183-2191

Abstract

Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (NCT02561988) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30-400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 x 10(9)/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited >= 50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1078-8956
• Sprache: Englisch