RMC-5552 in Adults with Recurrent Glioblastoma

Brain Cancer
Nicholas Butowski, MD
University of California, San Francisco


Despite current treatment with surgery, radiation, and chemotherapy, glioblastoma (GBM) will inevitably recur within 6 to 13 months of treatment. The median survival from recurrence is approximately 9 months. ​Furthermore, there is no standardized established therapy for progressive GBM. To address the dismal prognosis of patients with recurrent GBM, it is essential to investigate rational targeted agents.​ The PI3K/AKT/mTOR pathway is a crucial player in the development and progression of GBM. While this pathway is dysregulated in the majority of patients with GBM, drugs targeting the PI3K pathway have failed to be effective. Drugs that target mTOR have also failed to be effective as they only block one of downstream pathways or they do not bind to the target long enough. ​RMC-5552 is a selective ‘bi-steric’ inhibitor targeting both downstream pathways of mTORC1. This bi-steric mTORC1 inhibitor has also shown improved pharmacology. As a result, it binds to mTORC1 more potently, selectively, and durably. ​This phase I/II study will expand upon the SPORE project allowing for additional patients to determine the maximum tolerated dose and safety of RMC-5552 in patients with recurrent non-surgical GBM. ​After determining the recommended phase II dose, they will assess if pre-surgically administered RMC-5552 achieves biologically sufficient concentrations in patients with recurrent GBM who are eligible for surgery and expand RMC-5552 to patients with recurrent non-surgical GBM to evaluate its preliminary antitumor effect.​

​Trial Registration: ClinicalTrials.gov Identifier: NCT05557292