Phase 1 FT536 MICA/B-directed CAR-NK (MICA/MICB-targeted) for recurrent grade 4 astrocytoma

This single-center, first-in–cancer-type Phase 1, open-label, sequential dose-escalation study tests intratumoral FT536 in adults with recurrent WHO grade 4 astrocytoma (eligible regardless of IDH mutation status) when a repeat craniotomy for gross tumor resection is feasible at first or second recurrence. FT536 (Fate Therapeutics) is an allogeneic, iPSC-derived engineered NK-cell therapy that uses a MICA/MICB-targeted CAR to recognize stress ligands on tumor cells; it is also engineered with CD38 knockout, a high-affinity non-cleavable CD16 to enhance antibody-dependent cytotoxicity, and an IL-15/IL-15Rα fusion to support NK-cell persistence. The surgical schema includes biopsy to confirm recurrence, then a one-time 1 mL intratumoral injection of FT536 along the biopsy tract into enhancing (and sometimes nonenhancing) tumor, followed 7–14 days later by maximum safe resection and postoperative MRI safety assessment. The University of Minnesota’s Masonic Cancer Center is leading this work, with dose levels ranging from 1×10^7 to 6×10^7 cells. Today’s care after recurrence is individualized—repeat surgery when feasible plus options like re-irradiation, temozolomide rechallenge or lomustine, and bevacizumab for symptom control—so the key angle here is local delivery of an off-the-shelf engineered NK-cell product into the operative window to probe safety, immune effects, and early activity.