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

Summary

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.

Timeline

Start

2019-04-16

Primary completion

2027-06-23

Completion

2027-06-23

Publications

• Siebenhaar F, Broesby-Olsen S, Castells M, George TI, Livideanu CB, Alvarez-Twose I, Panse J, Barete S, Reiter A, Dybedal I, Akin C, Van Daele P, Radia DH, Cerquozzi S, Ustun C, Sabato V, Gotlib J, Rafferty M, DeAngelo DJ, Schafhausen P, Ungerstedt J, Ogbogu PU, Florell S, Wada DA, Rets A, Lin HM, Bidollari I, Hong J, Shaheen D, Lampson B, Hartmann K. Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study. J Am Acad Dermatol. 2026 Jun;94(6):1705-1713. doi: 10.1016/j.jaad.2026.02.025. Epub 2026 Feb 12.
• Worth S, George TI, Shaheen DJ, Roche M, Vachhani P. Chronic Anaphylaxis With Indolent Systemic Mastocytosis: A Case Report. Case Rep Hematol. 2025 Nov 6;2025:9562195. doi: 10.1155/crh/9562195. eCollection 2025.
• Gotlib J, Castells M, Elberink HO, Siebenhaar F, Hartmann K, Broesby-Olsen S, George TI, Panse J, Alvarez-Twose I, Radia DH, Tashi T, Bulai Livideanu C, Sabato V, Heaney M, Van Daele P, Cerquozzi S, Dybedal I, Reiter A, Pongdee T, Barete S, Ustun C, Schwartz L, Ward BR, Schafhausen P, Vadas P, Bose P, DeAngelo DJ, Rein L, Vachhani P, Triggiani M, Bonadonna P, Rafferty M, Butt NM, Oh ST, Wortmann F, Ungerstedt J, Guilarte M, Taparia M, Kuykendall AT, Arana Yi C, Ogbogu P, Gaudy-Marqueste C, Mattsson M, Shomali W, Giannetti MP, Bidollari I, Lin HM, Sulllivan E, Mar B, Scherber R, Roche M, Akin C, Maurer M. Avapritinib versus Placebo in Indolent Systemic Mastocytosis. NEJM Evid. 2023 Jun;2(6):EVIDoa2200339. doi: 10.1056/EVIDoa2200339. Epub 2023 May 23.
• Padilla B, Shields AL, Taylor F, Li X, Mcdonald J, Green T, Boral AL, Lin HM, Akin C, Siebenhaar F, Mar B. Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) in a phase 2 clinical study. Orphanet J Rare Dis. 2021 Oct 18;16(1):434. doi: 10.1186/s13023-021-02037-3.

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Indications