ACTR-45. FATTY ACID SYNTHASE INHIBITOR TVB-2640 INCREASES PROGRESSION FREE SURVIVAL IN RECURRENT GBM

Abstract

BACKGROUND: Standard of care for glioblastoma (GBM) is surgical resection followed by temozolamide, with bevacizumab (bev) given at relapse. Responses to bev remain brief; resistance may involve overexpression of Fatty Acid Synthase (FASN). METHODS: This is a prospective phase 2 study of bev with TVB-2640 in patients with rGBM at first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age ≥ 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. An exploratory phase randomization into 2 separate arms of single agent bev or in combination with TVB-2640 with MR-Spectroscopy (MRS) and serum sampling for exosome analysis obtained on all patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converged to a single arm and continue to receive bev in combination with TVB- 2640. A total sample size of 24 patients will provide 90% power to detect a 4 month difference in PFS (3-4 months for Bev alone (historic controls) (i.e., a hazard ratio of 0.43) using a one-sided log-rank test with alpha=0.1. RESULTS: Enrollment is complete with 28 patients to date. 3 failed screening. 21 came off study and 4 are active. No grade 4 or higher treatment-related AEs have occurred, with Grade 3 events included 3 cases of palmar-plantar erythrodysesthesia; 1 each of hypertension, stomatitis, optic neuritis, DVT, and wound infection. 95.2% of patients have achieved at least stable disease by RANO Criteria, with a 66.7% overall response rate (ORR). Median time to progression was 5.9, which is statistically superior to historical controls. Overall survival as well as biomarker analysis (exosome, MRS), is pending. CONCLUSIONS: The combination of TVB2640 with bev appears well tolerated and with PFS6 significantly improved over historical controls. Final data analysis as well as exploratory biomarker analysis will be presented.