P=N/A, N=80, Not yet recruiting, Blueprint Medicines Corporation

P1/2, N=37, Active, not recruiting, Blueprint Medicines Corporation | Trial primary completion date: Feb 2025 --> Nov 2025

Both patients underwent allogeneic hematopoietic stem cell transplantation, but subsequently developed refractory disease progression unresponsive to multiple salvage regiments. Strikingly, avapritinib intervention achieved unprecedented clinical responses in these complex cases.

Molecular analyses confirmed the KIT mutation in multiple non-infiltrated tissues, demonstrating the germline nature of the mutation. Despite targeted treatment with pharmacokinetically monitored midostaurin and adjunct therapies, the disease progressed rapidly, resulting in fatal multiorgan failure.

P2, N=251, Active, not recruiting, Blueprint Medicines Corporation | Trial completion date: Jan 2028 --> Jun 2027

APB and encorafenib (ECB as the internal standard) were separated using an isocratic mobile phase approach on an Agilent SB-C18 (reversed-phase) column. The metabolic stability characteristics including the intrinsic clearance and the in vitro half-life of APB were determined to be 22.11 mL min-1 kg-1 and 36.67 min, respectively. In silico analysis suggests that minor structural changes to the methyl pyrazole moiety in drug design may improve the metabolic stability and safety relative to APB.

P1/2, N=78, Recruiting, The First Affiliated Hospital of Soochow University

It covers the role of tyrosine kinase inhibitors (TKIs), specifically imatinib, and further treatment options, such as sunitinib, regorafenib, and ripretinib, as well as avapritinib for platelet-derived growth factor receptor alpha D842V mutations. In addition, this review emphasizes individualized treatment strategies within multidisciplinary expert teams, including surgery and other locoregional therapies, together with the importance of mutation-guided approaches, particularly for wild-type GISTs. Finally, it explores the potential of next-generation KIT inhibitors, combination therapies, and other investigational approaches.

Avapritinib extends PFS and OS among patients with PDGFRA D842V-mutant GIST in real-world practice, mirroring pivotal trial outcomes. Its substantial activity supports its use as a first-line therapy for this subgroup. The manageable safety profile reinforces avapritinib viability for routine use. Given the rarity of these cases, it is advised to consult sarcoma-expert units.

Our findings demonstrate that PDGFRA overexpression mediates lenvatinib resistance in HCC and that targeting PDGFRA with avapritinib, surmounts this resistance. Furthermore, the PTEN/AKT/GSK-3β/β-catenin pathway was implicated in lenvatinib resistance, providing a potential therapeutic strategy for HCC patients displaying lenvatinib resistance. Further clinical studies are warranted to validate these findings and to explore the clinical application of PDGFRA-targeted therapies in HCC treatment.

P2, N=107, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed | Trial completion date: Jan 2026 --> Dec 2024 | Trial primary completion date: Jan 2026 --> Dec 2024