Update on the first phase I study of AGRO100 in advanced cancer

Abstract

3064 Background: AGRO100 is an oligonucleotide that functions as an aptamer and binds to nucleolin, a protein found intranuclear in all cells, but uniquely expressed on the surface of tumor cells. Such binding leads to internalization of the complex, and a strong anti-proliferative response in the tumor cell. Objectives of this study are to (1) determine the maximum-tolerated dose and dose-limiting toxicity of AGRO100 in patients with advanced cancer; (2) determine the pharmacokinetic distribution and profile of AGRO100; (3) obtain preliminary evidence of clinical and biological responses to AGRO100 therapy. Methods: AGRO100 was administered as continuous intravenous infusion in the hospital. Dose level 1 was 1 mg/kg/day over 4 days. Patients were enrolled in cohorts of 3. If no toxicity was observed 28 days after therapy, the dose of AGRO100 was increased up to 10 mg/kg/day over 7 days. Toxicity was graded by the NCI CTCAE v3.0. Responses were assessed every 28 days by using the RECIST guidelines. Results: From September 2003 through July 2004, 17 patients with advanced cancer were enrolled. Prior to AGRO100 treatment, all patients had objective documentation of progressive metastatic disease after multiple therapies. Patient characteristics: median age 63 (30 - 74), PS ECOG 1 (0 - 2). Type of cancer: renal (3), colon (3), pancreatic (2), and lung, lymphoma, gastric, cervical, melanoma, prostate, synovial sarcoma, hemangiopericytoma (1 each). All patients are evaluable for toxicity and response. 22 cycles of AGRO100 have been administered (1–2 cycles/patient). Eight (50%) patients had stable disease at two months after treatment; disease was stable in these patients for 2 - 9 months before progression. One patient is maintaining a near complete response after more than 6 months. No toxicity of any type related to drug administration has been observed. AGRO100 was present in the serum during the entire infusion and the concentration was related to the dose. Conclusions: AGRO100 is the first nucleic acid aptamer ever tested for the treatment of cancer in humans. This non-toxic targeted cancer therapy is showing very promising responses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aptamera