Ncctg N1174: Phase I/Comparative Randomized Phase (Ph) Ii Trial Of Trc105 Plus Bevacizumab Versus Bevacizumab In Recurrent Glioblastoma (Gbm) (Alliance).

2023Background: TRC105 is a humanized antibody targeting CD105 (endoglin), a member of the TGFβ receptor superfamily. CD105 is expressed in glioma stem cells and circulating endothelial cells (CECs) in GBM patients (pts), increasing following VEGF inhibition. N1174 was conducted in recurrent bevacizumab (bev) naive GBM pts to investigate the hypothesis that CD105 blockade+bev can delay development of bev resistance. Methods: After a ph I cohort (15 pts) established the ph II dose of TRC105 as 10 mg/kg IV over 4 hours every 7 days in combination with standard dose bev, the ph II trial used 1:1 randomization with 90% power and 0.10 type I error to detect a 3 month (mo) difference in progression-free survival (PFS) between the two arms. CECs including CD105 positive subsets were measured by flow cytometry at baseline and multiple time points. Results: Based on 101 evaluable ph II pts, there was no significant difference in PFS between TRC105+bev and bev only (2.9 vs 3.2 mo, respectively; HR=1.14, 95% CI 0.73...