Abstract CT023: PATHFINDER: Interim analysis of avapritinib (ava) in patients (pts) with advanced systemic mastocytosis (AdvSM)

Introduction: Systemic mastocytosis is a clonal, hematologic neoplasm driven by KIT D816V mutation in >90% of cases, with limited treatment options. In a phase I study, ava, a potent inhibitor of KIT D816V, induced durable responses which deepened over time in pts with AdvSM, regardless of prior therapy or AdvSM subtype. PATHFINDER (NCT03580655) is a pivotal open-label, single-arm phase II study of ava in pts with AdvSM. Methods: Pts were aged ≥18 years with centrally confirmed diagnosis of an AdvSM subtype. Primary endpoint was overall response rate (ORR) by modified International Working Group-Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis criteria. This pre-specified interim analysis included 32 response-evaluable pts. Secondary endpoints included mean baseline change in AdvSM-Symptom Assessment Form Total Symptom Score (TSS) (Gotlib J et al. ASH 2018) and safety. Results: At June 23, 2020, 62 pts with AdvSM received ava primarily at 200 mg orally once daily (QD). Median age was 69 years (range 31-88), 31% had ECOG PS 2-3, and 68% had prior systemic treatment (55% with midostaurin). At 10.4 months median follow-up, 52/62 (84%) pts remained on treatment. ORR was 75% (95% CI 57-89; P=1.6×10-9) in 32 response-evaluable pts. Complete remission with full or partial hematologic recovery occurred in 19% of pts. Median time to response was 2 months; responses deepened over time. Median overall survival (OS) was not reached; estimated 12-month OS was 87%. There were ≥50% reductions from baseline serum tryptase (87%; n=54), marrow mast cell aggregates (71%; n=44), and KIT D816V allele fraction (53%; n=33). Mean TSS at baseline (n=56) was 18.3; fatigue, spots, itching, flushing, and abdominal pain were the most severe symptoms. Mean change in TSS was -7.7 (1-sided P Citation Format: Daniel J. DeAngelo, Andreas Reiter, Deepti Radia, Michael W. Deininger, Tracy I. George, Jens Panse, Alessandro M. Vannucchi, Madlen Jentzsch, Ivan Alvarez-Twose, Andrzej Mital, Olivier Hermine, Ingunn Dybedal, Elizabeth O. Hexner, Lisa K. Hicks, Lambert Span, Ruben Mesa, Prithviraj Bose, Kristen M. Pettit, Mark L. Heaney, Stephen Oh, Jayita Sen, Hui-Min Lin, Brenton G. Mar, Jason Gotlib. PATHFINDER: Interim analysis of avapritinib (ava) in patients (pts) with advanced systemic mastocytosis (AdvSM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT023.