Phase I study of TRC105 (anti-CD105 [endoglin] antibody) therapy in patients with advanced refractory cancer.
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.3013
ISSN1527-7755
AutoresDavid S. Mendelson, Michael Gordon, Lee S. Rosen, Herbert I. Hurwitz, M. K. Wong, B. J. Adams, Daniel Esteban Pineda Alvarez, Ben K. Seon, Charles P. Theuer, B. R. Leigh,
Tópico(s)Cancer Cells and Metastasis
Resumo3013 Background: CD105 (endoglin) is an angiogenic membrane protein that is highly expressed on the proliferating vasculature of solid tumors and up-regulated following anti-VEGF therapy. TRC105 is a human/murine chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth via endothelial cell growth inhibition, ADCC, and apoptosis. Methods: The safety and PK of TRC105 were evaluated in pts with refractory cancer at dose levels from 0.01 to 1 mg/kg every 2 weeks using TRC105 produced in NS0 cells and then at 0.3 and 1 mg/kg using TRC105 with increased ADCC activity produced in a high-expressing CHO cell line. TRC105 was escalated in cohorts of 3-6 pts. Results: 33 ECOG PS 0-1 pts received TRC105 at doses between 0.01-1.0 mg/kg. Two dose-limiting toxicities (DLT) were reported in pts who received TRC105 produced in NS0 cells: one pt experienced grade 4 gastric ulcer bleeding at 0.1 mg/kg on day 4 which resolved spontaneously and one pt experienced grade 3 infusion reaction (without premedication). Infusion reactions were also noted in the initial two pts dosed at 0.3 mg/kg using TRC105 produced in CHO cells, including one grade 3 DLT. The protocol was amended to increase the infusion time from 1 to 4 hours and mandate premedication. Four pts were subsequently dosed at 0.3 mg/kg and six pts were dosed at 1 mg/kg without DLT following amendment. One pt with castrate- refractory prostate cancer remains on study after 20 months of TRC105 at 0.01 mg/kg with a complete PSA response and bone scan normalization. In addition, 6-month stable disease was seen in a pt with ovarian cancer (CA125 decrease of 16%). Best response also included stable disease > 2 months (n=9) and progression (n=18). Serum TRC105 concentrations expected to saturate CD105 binding sites (> 0.2 ug/mL) were achieved at a dose of 0.3 mg/kg, and concentrations > 10 ug/mL were achieved at 1.0 mg/kg. HAMA became detectable in 2 of 29 pts. Conclusions: TRC105 is tolerated at doses with evidence of clinical activity. Additional monotherapy and combination studies are planned. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration TRACON Pharma TRACON Pharma TRACON Pharma
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