A phase I study of TRC105 (anti-CD105 monoclonal antibody) in metastatic castration-resistant prostate cancer (mCRPC)

Autor: D. Adelberg, A. B. Apolo, R. A. Madan, J. L. Gulley, A. Pierpoint, D. R. Kohler, J. B. Trepel, S. M. Steinberg, W. D. Figg, W. L. Dahut
Rok vydání: 2011
Předmět:
Zdroj: Journal of Clinical Oncology. 29:171-171
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2011.29.7_suppl.171
Popis: 171 Background: TRC105 is a human/murine chimeric IgG1 monoclonal antibody to CD105 (endoglin) that inhibits angiogenesis and tumor growth through inhibition of endothelial cell (EC) proliferation, antibody-dependent cellular cytotoxicity and induction of apoptosis. CD105 is highly expressed on proliferating vascular ECs. Preclinical and clinical evidence demonstrates an important role for angiogenesis in mCRPC biology. Methods: The primary objective is to evaluate safety and identify the maximum tolerable dose of TRC105. Secondary objectives include the assessment of TRC105 pharmacokinetics, PSA response rate and overall response rate (ORR). Eligibility requires ECOG performance status (PS) ≤ 2 and progressive mCRPC. Three cohorts of 3-6 patients receive TRC105 at doses of 1, 3 or 10 mg/kg IV over 1–4 hours every 2 weeks of a 4 week cycle. Premedications are dexamethasone, acetaminophen, famotidine, and diphenhydramine. PSA is evaluated prior to each treatment and response is assessed every 2 cycles with imaging studies. Results: Eight patients are enrolled in cohorts 1–3. Median age is 65 (range 47–84), ECOG PS 1 (1–2), Gleason score 8 (6–10), on–study PSA 201 (0.10 – 3,373), and number of prior therapies after gonadotropin-releasing hormone agonist or anti-androgen therapy 2.5 (0–6). Median time on study is 14 weeks (7–16). Dose-limiting toxicity was not observed. Grade 1 to 2 infusion reactions occurred in 4 patients. PSA declines were seen in both patients in cohort 3 (26% and 51% from baseline); each had progressed on docetaxel and at least one second-line agent. Five of 6 evaluable patients with measurable soft tissue disease achieved stable disease (2 in cohort 1, 2 in cohort 2 and 1 in cohort 3); the latter 3 patients in cohorts 2 and 3 remain on study. Conclusions: TRC105 is tolerated at doses up to 10 mg/kg every 2 weeks with early evidence of clinical activity in patients with mCRPC. Accrual is ongoing to evaluate higher doses and more frequent dosing. No significant financial relationships to disclose.
Databáze: OpenAIRE
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