Xospata (gilteritinib)

This case suggests that AML harboring rare FLT3-JMD point mutations may exhibit transient dependence on FLT3 signaling and may respond to FLT3 inhibition despite the absence of canonical FLT3 alterations. These findings highlight the potential value of extended molecular profiling and longitudinal genomic assessment to identify potential therapeutic targets and mechanisms of resistance in relapsed AML.

The multi-national phase 1/2 SKIPPER study evaluated gilteritinib combined with fludarabine and cytarabine chemotherapy and granulocyte colony‑stimulating factor (FLAG) in children and adolescents/young adults with relapsed/refractory FLT3‑ITD AML. The gilteritinib and FLAG regimen had manageable safety, induced high remission rates, and enabled allogeneic hematopoietic stem cell transplant for several patients. Although limited by a small sample size, these findings support further evaluation of gilteritinib in pediatric patients with FLT3-mutated AML, particularly in frontline settings (ClinicalTrials.gov Identifier: NCT04240002).

P3, N=276, Active, not recruiting, Astellas Pharma Inc | Trial completion date: Mar 2026 --> Mar 2027

Co‑culture and rescue experiments suggested the mechanism involved inhibiting PD‑L1 and CD8 co‑expression, corroborated by animal experiments. Gilteritinib can overcome alectinib resistance and inhibit PD‑L1 and CD8 co‑expression in ALK‑rearranged NSCLC, providing a new therapeutic strategy.

In a Ba/F3 FLT3-ITD-F691L mouse model, nintedanib demonstrated superior anti-leukemic efficacy compared with gilteritinib and quizartinib. Furthermore, nintedanib potently inhibited primary AML blasts harboring FLT3-ITD while normal bone marrow remained intact. These findings identify nintedanib as a promising FLT3 inhibitor and support its further therapeutic investigation in FLT3-ITD-positive AML.

P2, N=205, Recruiting, Ruijin Hospital

P=N/A, N=65, Recruiting, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital; Chinese Academy of Medical Sciences, Peking Union Medical College Hospital

P=N/A, N=60, The First Hospital of China Medical University; The First Hospital of China Medical University

We experimentally validated several actionable findings, including tepotinib to target the IRAK1/4-cholesterol pathway in glioblastoma, brigatinib to target the MARK2/3-Hippo pathway in pancreatic cancer and gilteritinib to overcome MET mutation-driven drug resistance and metastasis. To facilitate exploration of our data, we provide KIRHub, a web-based tool that allows identification of existing inhibitors of wild-type and mutated kinases to guide precision oncology.

Subsequently, the CML burden declined as the AML clone regrew. This case highlights the importance of accurately assessing clonal changes using genetic analysis when implementing molecular targeted therapy for hematologic malignancies.