(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis

Summary

This is an open-label, single arm, Phase 2 study evaluating the efficacy and safety of avapritinib (BLU-285) in patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive SM (ASM), SM with associated hematologic neoplasm (SM-AHN), and mast cell leukemia (MCL)

Timeline

Start

2018-11-21

Primary completion

2024-12-18

Completion

2024-12-18

Outcome

Met primary endpoint

registry analysis (superiority test); Avapritinib; p < 0.0001; Wald Test NCT03580655 ↗

paper The primary endpoint was successfully met (P = 1.6 × 10-9), with an ORR of 75% PMID 34873345 ↗

Publications

• Gotlib J, Reiter A, Radia DH, Alvarez-Twose I, Deininger MW, George TI, Panse J, Mital A, Pettit KM, Vannucchi AM, Platzbecker U, Hermine O, Elshoury A, Livideanu CB, Mesa R, Ustun C, Triggiani M, Dybedal I, Jurcic JG, Zanotti R, Oh ST, Yacoub A, Hexner EO, Bose P, Lee SG, Sperr WR, Griffiths EA, Butler M, Lubke J, Bidollari I, Lin HM, Rylova S, Dimitrijevic S, Munoz-Gonzalez JI, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study. Blood Adv. 2026 May 26;10(10):3676-3689. doi: 10.1182/bloodadvances.2025017519.
• Reiter A, Gotlib J, Alvarez-Twose I, Radia DH, Lubke J, Bobbili PJ, Wang A, Norregaard C, Dimitrijevic S, Sullivan E, Louie-Gao M, Schwaab J, Galinsky IA, Perkins C, Sperr WR, Sriskandarajah P, Chin A, Sendhil SR, Duh MS, Valent P, DeAngelo DJ. Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis. Leukemia. 2022 Aug;36(8):2108-2120. doi: 10.1038/s41375-022-01615-z. Epub 2022 Jul 5.
• Reiter A, Schwaab J, DeAngelo DJ, Gotlib J, Deininger MW, Pettit KM, Alvarez-Twose I, Vannucchi AM, Panse J, Platzbecker U, Hermine O, Dybedal I, Lin HM, Rylova SN, Ehlert K, Dimitrijevic S, Radia DH. Efficacy and safety of avapritinib in previously treated patients with advanced systemic mastocytosis. Blood Adv. 2022 Nov 8;6(21):5750-5762. doi: 10.1182/bloodadvances.2022007539.
• Gotlib J, Reiter A, Radia DH, Deininger MW, George TI, Panse J, Vannucchi AM, Platzbecker U, Alvarez-Twose I, Mital A, Hermine O, Dybedal I, Hexner EO, Hicks LK, Span L, Mesa R, Bose P, Pettit KM, Heaney ML, Oh ST, Sen J, Lin HM, Mar BG, DeAngelo DJ. Efficacy and safety of avapritinib in advanced systemic mastocytosis: interim analysis of the phase 2 PATHFINDER trial. Nat Med. 2021 Dec;27(12):2192-2199. doi: 10.1038/s41591-021-01539-8. Epub 2021 Dec 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Avapritinib	Small molecule	200 mg	Oral

Indications