Dr Radia on the Continued Investigation of Elenestinib in Indolent Systemic Mastocytosis

What we found from the [part] 1 data [from the HARBOR trial] was that the best the dose to move forward...was 75 mg of elenestinib once daily. We've got that dose sorted, and the second thing was that, again, the safety profile was pretty good across the all the cohorts.

Deepti Radia, MBBS, BSc, MRCPI, FRCPath, MSc Med Ed, a consultant hematologist, chair of the London Specialist Training Committee, and chair of the National Specialist Advisory Committee in Hematology at Guy's and St Thomas' NHS Foundation Trust, discussed the ongoing phase 2/3 HARBOR trial (NCT04910685) evaluating the next-generation, KIT D816V inhibitor elenestinib (BLU-263) in patients with indolent systemic mastocytosis.

With a high incidence of KIT D816V mutations across the systemic mastocytosis population, targeting these alterations remains a key therapeutic strategy in ongoing research. Part 1 of the HARBOR trial served as the dose-finding portion of the study, where patients were randomly assigned in a 1:1:1:1 fashion to receive placebo plus best supportive care (BSC; n = 10); elenestinib at 25 mg per day plus BSC (n = 10); elenestinib at 50 mg per day plus BSC (n = 10); or elenestinib at 100 mg per day plus BSC (n = 9).

Previously reported findings from part 1 showed that elenestinib was well tolerated across dose levels, and all 3 dose levels were associated with improvements in biomarkers of disease burden compared with placebo.

Part 2 of HARBOR will include approximately 350 patients, who are being randomly assigned 2:1 to receive elenestinib at 75 mg per day or placebo for up to 48 weeks in a double-blinded fashion. Radia noted the unlike the phase 3 PIONEER trial (NCT03731260), which investigated avapritinib (Ayvakit) in patients, HARBOR will also feature nonrandomized cohorts of patients who have received prior treatment with a KIT D816V inhibitor, who will receive elenestinib at 75 mg per day, with optional escalation to 100 mg. Another cohort will include patients with smoldering systemic mastocytosis, who will receive elenestinib at 100 mg per day.