Final results from a phase I study of TRC093 (humanized anti-cleaved collagen antibody) in patients with solid cancer.
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.3038
ISSN1527-7755
AutoresFrancisco Robert, Michael Gordon, Lee S. Rosen, David S. Mendelson, Marilyn Mulay, B. J. Adams, Delia Alvarez, Charles P. Theuer, B. R. Leigh,
Tópico(s)Angiogenesis and VEGF in Cancer
Resumo3038 Background: TRC093 is a humanized IgG1 monoclonal antibody to cryptic collagen epitopes that are exposed during angiogenesis and tumor growth. These epitopes are recognized by integrin receptors on endothelial and cancer cells during angiogenesis and tumor progression. Intravenous TRC093 localizes to the subendothelial basement membranes in tumor tissues (but not normal tissues) and inhibits angiogenesis and tumor growth as monotherapy and in combination with bevacizumab. Methods: This phase I study evaluated the safety and PK of i.v. TRC093 monotherapy for advanced refractory cancer. Patients were required to have an ECOG PS ≤ 2 and adequate organ function. TRC093 was administered by 90 min i.v. infusion on days 1 and 15 of each 28-day cycle. Results: A total of 19 patients were treated including 3 each at 0.5, 1.5, and 5 mg/kg, 9 at 12 mg/kg, and 1 at 24 mg/kg. The median number of prior cancer regimens was 4 (range: 1 to 10). Dose-limiting toxicity was not observed. The 12 mg/kg dose level was considered the maximum feasible dose due to limited drug supply. The most common possibly related adverse event was grade 1/2 fatigue. Possibly related grade 3/4 adverse events were not observed. One patient experienced grade 1 infusion reaction with the initial dose that did not recur with diphenhydramine premedication. TRC093 demonstrated linear dose-dependent PK typical of a humanized antibody. Target TRC093 serum concentrations based on preclinical efficacy studies were achieved throughout the 2-week dosing interval at 12 mg/kg (mean Cmax=467 ug/mL, T1/2=10.9 days). Human antihuman antibody (HAHA) formation was not observed. Evidence of clinical activity included one ovarian cancer patient with a mixed response, five patients with stable disease lasting up to 10 months, and an overall decline in mean circulating VEGF levels with treatment. Conclusions: TRC093 was well-tolerated at clinically relevant doses with early evidence of activity. Phase Ib/II trials are planned to evaluate TRC093 in combination with bevacizumab in patients with glioblastoma. 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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