Phase 1 study of intracranial T cell therapy with pemetrexed for refractory brain metastases and glioblastomas

Therapeutic options remain limited for advanced intracranial malignancies, including brain metastases and glioblastomas, particularly in patients ineligible for surgery, radiotherapy, or systemic therapies. This phase 1 study evaluates the safety and feasibility of intracranial administration of low-dose pemetrexed followed by RetroNectin-activated killer cells (RAKs) and interleukin 2 via an Ommaya reservoir (collectively referred to as SCOPE-T) in 25 patients with refractory intracranial malignancies. Nineteen patients completed at least one treatment cycle, and 17 received the maximum tested RAK dose (5 × 108 cells). Treatment is well tolerated, with no treatment-related adverse events greater than grade 2; transient fever and headache are the most common toxicities. Exploratory radiographic and clinical assessments suggest disease stabilization in evaluable patients. These findings support the feasibility and safety of intracranial SCOPE-T and indicate preliminary signals of therapeutic activity. Given the small sample size and non-randomized design, the results should be interpreted as exploratory