NCCTG N1174: Phase I/comparative randomized phase (Ph) II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma (GBM) (Alliance).

• DOI: 10.1200/jco.2017.35.15_suppl.2023
• Publication Date: 2018-09-06T15:41:11Z
• Authors: Evanthia Galanis; S. Keith Anderson; Nicholas A. Butowski; Adilia Hormigo; David Schiff; David Dinh Tran; Antonio Marcilio ...; Kurt A. Jaeckle; Shaji Kumar; Timothy J. Kaufmann; Jan C. Buckner; Erin Twohy; Caterina Giannini; Patrick Y. Wen
• Keywords: Progression-free survival

2023 Background: TRC105 is a humanized antibody targeting CD105 (endoglin), member of the TGFβ receptor superfamily. expressed in glioma stem cells and circulating endothelial (CECs) GBM patients (pts), increasing following VEGF inhibition. N1174 was conducted recurrent bevacizumab (bev) naïve pts to investigate hypothesis that blockade+bev can delay development bev resistance. Methods: After ph I cohort (15 pts) established II dose as 10 mg/kg IV over 4 hours every 7 days combination with standard bev, trial used 1:1 randomization 90% power 0.10 type error detect 3 month (mo) difference progression-free survival (PFS) between two arms. CECs including positive subsets were measured by flow cytometry at baseline multiple time points. Results: Based on 101 evaluable pts, there no significant PFS TRC105+bev only (2.9 vs 3.2 mo, respectively; HR=1.14, 95% CI 0.73-1.77, p=0.57), or overall (10.0 7.4 mo; HR 1.02 0.63-1.65, p=0.93). Response rate (complete partial) 12.2% (6/49) for 11.6% (5/43) only. Overall incidence grade (gr) 3+ toxicity higher (67.3% 32.7%, p<0.001) mainly due 14 gr anemia arm 0 pts. Gr non-heme toxicities receiving (50% 30.6%, p=0.07), headache (6 1 hyperglycemia (3 pts). remained stable treated suggesting possible impact anti-CD105 blockade, but increased progression arm. There association initial changes CEC values, independent treatment received. Conclusions: plus did not prolong median single agent although it associated non-significant prolongation OS. These data correlative analysis from study point against endoglin being clinically factor Support: U10CA180821, U10CA180882. Clinical information: NCT01648348.