Phase 1/2a study of once daily oral BAL101553, a novel tumor checkpoint controller (TCC), in adult patients with progressive or recurrent glioblastoma (GBM) or high-grade glioma.

• DOI: 10.1200/jco.2019.37.15_suppl.2025
• Publication Date: 2019-05-27T15:57:46Z
• Authors: Juanita Suzanne L...; Rebecca Sophie Kr...; Robert Rulach; Noor Md Haris; Mariana Scaranti; Paul James Mulhol...; Donna Crawford; Saira Bashir; Caterina Aversa; Alison L. Hannah; Stephanie Anderson; Marc Engelhardt; Thomas Kaindl; Patrice Larger; Phil McKernan; TR Jeffry Evans; Elizabeth Plummer
• Keywords: Temozolomide

2025 Background: BAL101553 (prodrug of BAL27862) is a novel TCC that promotes tumor cell death by modulating the spindle assembly checkpoint. BAL27862 lipophilic, small molecule shown in rodents to penetrate brain (brain/plasma ratio around unity), with promising antitumor activity orthotopic preclinical GBM models as monotherapy or combination radiotherapy (RT) without temozolomide. In this ongoing study (NCT02490800, CDI-CS-002), daily oral was initially examined solid-tumor patients, an MTD 16 mg/d and DLTs G4 hyponatremia G2 hallucinations (Lopez 2018, JCO 36, suppl. A2530). Subsequently expanded including separate cohort patients progressive recurrent high-grade glioma (Ingles Garces 2017, 35, TPS2601). Methods: Patients histologically-confirmed glioma, disease after prior RT with/without chemotherapy, received once-daily (28-day cycles) 3+3 dose-escalation design determine maximum tolerated dose (MTD). Adverse events were assessed CTCAE v4.03 grade (G), response RANO every two cycles. Pharmacokinetics (PK) evaluated on Day 1 Cycles 2. Results: study, 23 pts (13M/10F; median age 50 y), (min–max) number regimens = 2 (1–5), doses 8, 15, 20, 25 30 mg once daily. One DLT reversible depression fatigue occurred at 20 mg. Both mean Cmax AUC increased between 8 The PK exposure lower than for solid particular At (n 3), one patient IDH-mutated had partial (63% area reduction per RANO) continues > months, another stable 5 months. 15–20 mg/d, observed 3/10 patients. Conclusions: current data suggest well levels above established advanced tumors, shows indications clinical activity. Clinical trial information: 02490800.