The U.S. Food and Drug Administration (FDA) has granted accelerated approval to dordaviprone (Modeyso) for the treatment of adult and pediatric patients aged one year and older with pretreated diffuse midline glioma harboring the H3K27M mutation. This marks the first FDA-approved drug specifically indicated for this rare and aggressive brain cancer. Additionally, the FDA has fast-tracked zongertinib, developed by Boehringer Ingelheim, for nonsquamous non-small cell lung cancer (NSCLC) patients with HER2 tyrosine kinase domain (TKD) mutations. The agency also granted orphan drug designation to SH-110, a liquid formulation designed for glioma patients who have difficulty swallowing. In other developments, mirdametinib received FDA approval in February 2025 for neurofibromatosis type 1-associated plexiform neurofibromas, the first treatment indicated for this condition. The FDA also granted Regenerative Medicine Advanced Therapy (RMAT) designation to a novel CAR T-cell therapy for relapsed/refractory mantle cell lymphoma. Furthermore, the FDA has given a speedy review to birelentinib, a dual BTK/LYN inhibitor, for resistant chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). These approvals and designations highlight ongoing innovation in oncology therapeutics, with implications for improving outcomes in rare and difficult-to-treat cancers.