RBTT-01. A PHASE 2 TRIAL WITH ABI-009 (NAB-SIROLIMUS) AS SINGLE-AGENT AND COMBINATIONS IN RECURRENT HIGH-GRADE GLIOMA (rHGG) AND IN NEWLY DIAGNOSED GLIOBLASTOMA (ndGBM)

Abstract

BACKGROUND: The mTOR pathway is frequently activated in patients with GBM and is associated with reduced survival, making this pathway a promising target. However, mTOR inhibitors, including everolimus and temsirolimus, have poor brain penetration, limiting their potential use for GBM. ABI-009 is a novel albumin-bound mTOR inhibitor that has a distinct PK profile and biodistribution, including CNS penetration. The goal of this prospective, multi-cohort open-label phase 2 study is to evaluate the efficacy and safety of ABI-009 monotherapy and combination therapy in rHGG and ndGBM. METHODS: Eligible patients are ≥18 years old, KPS score ≥70, and have histologically confirmed rHGG or ndGBM. Arm A has 5 cohorts in patients with rHGG, naive to mTOR inhibitors: 1) ABI-009 single agent IV 100 mg/m2; 2-5) ABI-009 60mg/m2 plus TMZ 50mg/m2 or BEV 5mg/ kg or marizomib 0.8mg/m2 or CCNU 90mg/m2. In Arm B for patients with ndGBM, ABI-009 100mg/m2 is given weekly for 4 weeks (Induction) after surgery, followed by ABI-009 at 60mg/m2 plus RT/TMZ. Up to 19 patients per cohort will be enrolled: initial 9 patients with a stopping rule that only if there are ≥2 responses will the study proceed to further enrollment of the next 10 patients (Simon's 2-stage design). Treatment will continue until disease progression or unacceptable toxicity. The primary endpoint for all cohorts is overall response rate per RANO criteria; secondary endpoints are median PFS and OS, 6-month and 12-month PFS, 12-month OS, and safety.