887P - TRC105 (anti-endoglin antibody) in combination with bevacizumab (BEV) and as a single agent for platinum resistant ovarian cancer

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Ovarian Cancer
Presenter Agustin Garcia
Citation Annals of Oncology (2014) 25 (suppl_4): iv305-iv326. 10.1093/annonc/mdu338
Authors A.A. Garcia1, V. Makker2, D.L. Spitz3, D.E. Matei4, A.M. Nick5, C.N. Landen6, E.A. Alvarez7, D.S. Mendelson8, R.M. Strother4, B.K. Seon9, D. Alvarez10, B.J. Adams10, C.P. Theuer11, M.S. Gordon12
  • 1Norris Comprehensive Cancer Center, University of Southern California, 90033 - Los Angeles/US
  • 2Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York/US
  • 3Florida Cancer Specialists, Florida Cancer Specialists, Palm Beach/US
  • 4Medicine, Indiana University, Indianapolis/US
  • 5Md Anderson Cancer Center, The University of Texas, Houston/US
  • 6Division Of Gynecologic Oncology, University of Alabama Birmingham, Birmingham/US
  • 7Department Of Reproductive Medicine Division Of Gynecologic Oncology, University of California San Diego, San Diego/US
  • 8Pinnacle Oncology Hematology, Pinnacle Oncology Hematology, Scottsdale/US
  • 9Department Of Immunology, Roswell Park Cancer Institute, Buffalo/US
  • 10Clinical Operations, TRACON Pharmaceuticals, San Diego/US
  • 11Clinical Development, TRACON Pharmaceuticals, San Diego/US
  • 12Pinnacle Oncology Hematology, Oncology Research Associates, Scottsdale/US

Abstract

Aim

Endoglin (CD105) is an endothelial cell membrane receptor densely expressed on tumor vessels that is essential for angiogenesis and upregulated by hypoxia and VEGF inhibition. TRC105 is an anti-endoglin monoclonal antibody that potentiates BEV in preclinical models.

Methods

Patients with advanced metastatic ovarian cancer, ECOG PS 0-1, and normal organ function were treated with escalating doses of IV TRC105 (3, 6, 8 or 10 mg/kg/wk) plus BEV at 15 mg/kg q3wk or 10 mg/kg q2wk (n = 11) or with 10 mg/kg/wk TRC105 as a single agent (n = 23). Patients were assessed for safety, pharmacokinetics and response.

Results

TRC105 was well tolerated as a single agent in 23 patients with advanced platinum resistant ovarian cancer (median age = 63; median 2 prior therapies; range 1-5). The combination of TRC105 and BEV was well tolerated at the recommended single agent doses (10 mg/kg) when the initial dose of TRC105 was divided over two days to limit the frequency of headache. The concurrent administration of BEV and TRC105 did not otherwise potentiate known toxicities of TRC105 or BEV. Target TRC105 serum concentrations were achieved in all patients who received the combination or single agent TRC105 at 10 mg/kg. Mucocutaneous telangiectasia, a marker of TRC105 target modulation, was observed at higher rates with the combination of the two drugs (64% vs 35%; p = 0.15). Reductions in CA-125 were noted in 7 of 20 patients treated with TRC105 as a single agent and 7 of 11 treated with the combination, including 5 of 8 patients who received prior BEV or VEGF receptor tyrosine kinase inhibitor (VEGFR TKI) therapy. Radiographic reductions in tumor volume were observed in 7 of 11 patients (64%) treated with the combination including 4 of 8 patients who received prior BEV or VEGFR TKI, including two patients with PFS > 6 months; one of whom had a partial response by RECIST 1.1.

Conclusions

TRC105 10 mg/kg wkly was well tolerated with and without BEV 10 mg/kg q2wk in patients with advanced platinum resistant ovarian cancer. The combination demonstrated activity in BEV and VEGFR TKI refractory patients.

Disclosure

A.A. Garcia: The institution received funding for participating in the study; E.A. Alvarez: Dr. Alvarez receives compensation from TRACON Pharmaceuticals, Inc for service on the Safety Review Board Committee; D.S. Mendelson: Institution received funding to conduct the study; B.K. Seon: I am an inventor of TRC105. I do not own stock of TRACON Pharma. I am not a member on the advisory board or board of directors of TRACON Pharma. I had a corporate-sponsored research agreement with TRACON Pharma; D. Alvarez, B.J. Adams and C.P. Theuer: I am employed by TRACON Pharma and own stock in the company. M. Gordon: Institution received funding to conduct the study. All other authors have declared no conflicts of interest.