Blueprint Medicines announced AYVAKIT data showing high, durable response rates and prolonged overall survival in patients with advanced systemic mastocytosis, including SM with an associated hematological neoplasm. Long-term follow-up of 38 treatment-naive patients from the PATHFINDER trial and 69 patients from the EXPLORER trial – regardless of line of therapy – further validate the clinical efficacy and safety profile of AYVAKIT in advanced SM. Based on modified IWG-MRT-ECNM criteria, the overall response rate was defined as complete remission with full or partial recovery of peripheral blood counts, partial remission or clinical improvement. All responses were confirmed. In the PATHFINDER trial, AYVAKIT showed broad clinical activity in treatment-naive patients evaluable for response, including those with SM-AHN, as of a data cutoff date of April 20, 2021. For treatment-naive patients across advanced SM subtypes: ORR was 84 percent and CR/CRh rate was 32 percent. Median time to response was two months and median time to CR/CRh was six months. Median duration of response has not been reached. Estimated 24-month OS rate was 88 percent. For treatment-naive patients with SM-AHN: ORR was 95 percent and CR/CRh rate was 37 percent. Estimated 24-month OS rate was 86 percent. In addition, improvements were observed across hematologic parameters, such as monocytes and eosinophils in the peripheral blood, suggesting multi-lineage involvement of the KIT D816V mutation. In the EXPLORER trial, 57 patients across lines of therapy were evaluable for response as of a data cutoff date of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached in patients followed for up for six years. Safety data from the PATHFINDER and EXPLORER trials were consistent with previously reported results and the FDA approved labeling for AYVAKIT, and reinforce the favorable benefit-risk profile of AYVAKIT at the 200 mg once-daily recommended dose. The most common treatment-related adverse events included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naive patients since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy since the initiation of the EXPLORER trial in 2016. In addition, Blueprint Medicines announced top-line, 12-week results from the dose-finding Part 1 of the HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, reflecting the company’s long-term commitment to SM. HARBOR Part 1 was designed to assess concurrent dose cohorts of elenestinib plus best available therapy versus placebo plus best available therapy in patients with indolent SM. The trial included 29 patients in the elenestinib group, and 10 patients in the placebo group. Elenestinib showed evidence of clinical activity and safety consistent with its preclinical profile and a completed Phase 1 healthy volunteer trial. Elenestinib treatment led to rapid improvements in objective measures of mast cell burden, including serum tryptase and KIT D816V allele fraction, and total symptom score as measured by the Indolent SM Symptom Assessment Form. At 12 weeks, elenestinib demonstrated similar reductions in TSS across dose cohorts. In addition, consistent with previously reported data from the PIONEER trial of AYVAKIT in indolent SM, change in serum tryptase was not correlated with change in TSS. Safety results show that elenestinib was generally well-tolerated, and there were no discontinuations due to AEs. Blueprint Medicines plans to present data from Part 1 of the HARBOR trial at a medical congress in 2023.
Published first on TheFly
