RTID-08. A PHASE 1/2 STUDY OF SELINEXOR IN COMBINATION WITH STANDARD OF CARE THERAPY FOR NEWLY DIAGNOSED OR RECURRENT GLIOBLASTOMA (ndGBM OR rGBM)

Abstract

Abstract BACKGROUND GBM is the most common and most aggressive primary brain tumor with poor prognosis and median overall survival (mOS) of patients with ndGBM and rGBM being 15 vs 5-7 months, respectively. Selinexor is a first-in class, oral, selective nuclear export inhibitor which forces nuclear retention and reactivation of many tumor suppressor proteins. Selinexor with low dose dexamethasone was recently approved for patients with triple-class refractory multiple myeloma. Additionally, selinexor monotherapy has demonstrated broad activity in other hematologic and solid malignancies. In a Phase 2 study in rGBM (NCT01986348), selinexor demonstrated encouraging intratumoral penetration and single-agent efficacy at 80 mg once weekly with durable response and disease stabilization in heavily pretreated patients. Preclinical GBM studies showed synergy when combining selinexor with radiation, temozolomide and lomustine. METHOD This is a phase 1 (PH-1) dose finding study followed by a 1:1 randomized phase 2 (PH-2; n= 350) efficacy exploration trial to independently evaluate 3 different combination regimens: Arm A: radiation +/- selinexor in uMGMT ndGBM; Arm B: radiation and temozolomide +/- selinexor in MGMT ndGBM; Arm C:omustine +/- selinexor in first relapse rGBM following frontline radiation and temozolomide. The PH-1 primary endpoint is MTD/RP2D, with secondary endpoints of ORR per modified RANO, duration of response (DOR), PFS, and OS. The PH-2 primary endpoint for Arms A and B in ndGBM is PFS, with key secondary endpoints being OS, PFS6, ORR, DOR. For Arm C, the PH-2 primary endpoint is OS while key secondary endpoints are PFS, PFS6, ORR, DOR. The study has 70% power to detect a hazard ratio of 0.67 between selinexor and control for primary efficacy for arms A & B, and 80% power to detect a hazard ratio of 0.70 for arm C. We are currently enrolling patients nationwide. Clinical trial identifier: NCT04421378