Standard of care for glioblastoma (GBM) is surgical resection followed by chemoradiation and tumor treatment fields, with bevacizumab (bev) given at relapse. Responses to bev remain brief; and resistance may involve overexpression of Fatty Acid Synthase (FASN).
We performed prospective phase 2 study of bev with oral FASN inhibitor TVB-2640 in patients with rGBM at first relapse. Primary end point was progression free survival (PFS) with comparison to bev single agent outcomes from BELOB. Inclusion criteria included adults with 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 was 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 continued to receive bev in combination with TVB-2640.
A total of 28 patients were enrolled, 3 failed screening. 23 came off study and 2 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. A 66.7% overall response rate (ORR) was observed and 95% of patients have achieved at least stable disease by RANO Criteria. Median time to progression was 5.9m, which was statistically superior to historical controls. Median overall survival (OS) was 10.1m with an OS12 of 40%. Biomarker analysis (exosome, MRS) is pending.
The combination of TVB-2640 with bev appears well tolerated with improved progression free and overall survival compared to historical controls. Additional studies are warranted. Final data analysis as well as exploratory biomarker analysis will be presented.
Clinical trial identification
Legal entity responsible for the study
Mays Cancer Center at UTHSA.
Kolitz and Johnson Endowments for Neuro-Oncology Research.
All authors have declared no conflicts of interest.