CTNI-70. TPI 287, WHICH IN COMBINATION WITH BEVACIZUMAB (BEV) HAS SHOWN ACTIVITY IN PATIENTS WITH GLIOBLASTOMA (GBM) AFTER PRIOR THERAPY, TO BE EVALUATED IN A PHASE 2 TRIAL AS WELL AS IN OTHER CNS DISEASES

Abstract The abeotaxane TPI 287 is a microtubule stabilizing agent with demonstrated safety and preliminary evidence of activity in a Phase 1 combination study with BEV for recurrent GBM. (Goldlust 2024) This trial demonstrated a median overall survival (OS) of 13.4 months and 12 month OS of 64%, which is encouraging based on historical studies in this patient population. There was no ≥grade 1 neuropathy and 2 patients had grade 3 decreased neutrophil counts, indicating that TPI 287 was well tolerated. A Phase 2 trial of TPI 287 (200 mg/m2 every 3 weeks) + BEV (10 mg/kg every 2 weeks) is currently under developement based upon the recommended Phase 2 dose (RP2D) from the Phase 1 trial, The proposed U.S. multicenter trial will enroll patients with GBM at first recurrence and known MGMT methylation status. The primary endpoint is OS with secondary endpoints of overall response rate (ORR) and progression-free survival (PFS). Imaging will be subject to central review. Given the unique properties of TPI 287 to avoid blood brain barrier efflux, its safety profile, and demonstration of efficacy in GBM, several possibilities for further development, including strategies for metastatic tumors, e.g. triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) that are sensitive to these therapies and evaluation in a combination with radiation therapy, which is a standard of care for metastatic disease is being planned. We are also exploring the effect of this drug in a panel of pediatric brain tumors for feasibility of future clinical studies