Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)

Evanthia Galanis*, S. Keith Anderson, Erin Twohy, Nicholas A. Butowski, Adilia Hormigo, David Schiff, Antonio Omuro, Kurt A. Jaeckle, Shaji Kumar, Timothy J. Kaufmann, Susan Geyer, Priya U. Kumthekar, Jian Campian, Caterina Giannini, Jan C. Buckner, Patrick Y. Wen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM. Methods: Phase I dose-escalation/comparative randomized phase II trial in patients with GBM. During phase I, the maximum tolerated dose (MTD) of TRC105 in combination with bevacizumab was determined. In phase II, patients were randomized 1:1 to TRC105 and bevacizumab or bevacizumab monotherapy. Patients received TRC105 (10 mg/kg) weekly and bevacizumab (10 mg/kg) every 2 weeks. Efficacy, as assessed by progression-free survival (PFS), was the primary endpoint; safety, quality of life, and correlative outcomes were also evaluated. Results: In total, 15 patients were enrolled in phase I and 101 in phase II; 52 patients were randomized to TRC105 with bevacizumab and 49 to bevacizumab monotherapy. The MTD was determined to be 10 mg/kg TRC105 weekly plus bevacizumab 10 mg/kg every 2 weeks. An increased occurrence of grade ≥3 adverse events was seen in the combination arm, including higher incidences of anemia. Median PFS was similar in both treatment arms: 2.9 months for combination versus 3.2 months for bevacizumab monotherapy (HR = 1.16, 95% CI = 0.75-1.78, P =. 51). Quality of life scores were similar for both treatment arms. Conclusions: TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy.

Original languageEnglish (US)
Article numbervdac041
JournalNeuro-Oncology Advances
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2022

Keywords

  • angiogenesis
  • bevacizumab
  • CD105
  • glioblastoma
  • TRC105

ASJC Scopus subject areas

  • Clinical Neurology
  • Oncology
  • Surgery

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