elenestinib (BLU-263)

P1, N=20, Recruiting, Blueprint Medicines Corporation

Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.

P2/3, N=534, Recruiting, Blueprint Medicines Corporation | Trial completion date: Jun 2028 --> Sep 2032 | Trial primary completion date: Jun 2028 --> Sep 2032

P1, N=9, Terminated, Blueprint Medicines Corporation | N=67 --> 9 | Trial completion date: Dec 2025 --> Mar 2025 | Active, not recruiting --> Terminated; Terminated - alignment of strategic priorities

P1, N=67, Active, not recruiting, Blueprint Medicines Corporation | Recruiting --> Active, not recruiting | Phase classification: P1/2 --> P1 | Trial completion date: Nov 2029 --> Dec 2025 | Trial primary completion date: Nov 2029 --> Jan 2025

Avapritinib, the first licensed drug in SM capable of disease modification alongside the increasingly potent, oral and highly selective KIT tyrosine kinase inhibitors (TKIs) Bezuclastinib and now Elenestinib have enabled the prospect of long-term remissions...The importance of molecular profiling is being demonstrated in administering combination therapies for SM with an associated haematological neoplasm (AHN), allowing more personalised and streamlined treatment regimes. This review focuses on current management strategies of SM, focusing on state-of-the-art directed therapies, the evidence behind their use with presentation of two clinical cases to highlight key messages.

P2/3, N=443, Recruiting, Blueprint Medicines Corporation | Trial primary completion date: Aug 2023 --> Jun 2028

P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Initiation date: Apr 2023 --> Sep 2023

P1/2, N=67, Recruiting, Blueprint Medicines Corporation | Not yet recruiting --> Recruiting

P1/2, N=67, Not yet recruiting, Blueprint Medicines Corporation | N=108 --> 67 | Trial completion date: Nov 2027 --> Nov 2029 | Initiation date: Dec 2022 --> Apr 2023 | Trial primary completion date: Nov 2027 --> Nov 2029