Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy

Background NGR-hTNF consists of human tumour necrosis factor (hTNF) fused with the tumour-homing peptide Asp-Gly-Arg (NGR), which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. Preclinical antitumour activity was observed even at low doses. We evaluated the activity and safety of low-dose NGR-hTNF in colorectal cancer (CRC) patients failing standard therapies. Patients and methods Thirty-three patients with progressive disease at study entry received NGR-hTNF 0.8μg/m 2 given intravenously every 3weeks. The median number of prior treatment regimens was three (range, 2–5). One-quarter of patients had previously received four or more regimens and two-thirds targeted agents. Progression-free survival (PFS) was the primary study objective. Results NGR-hTNF was well tolerated. No treatment-related grade 3 to 4 toxicities were detected, most common grade 1 to 2 adverse events being short-lived, infusion-time related chills (50.0%). One partial response and 12 stable diseases were observed, yielding a disease control rate of 39.4% (95% CI, 22.9–57.8%). Median PFS and overall survival were 2.5months (95% CI, 2.1–2.8) and 13.1months (95% CI, 8.9–17.3), respectively; whereas in patients who achieved disease control the median PFS and overall survival were 3.8 and 15.4months, respectively. In an additional cohort of 13 patients treated at same dose with a weekly schedule, there was no increased toxicity and 2 patients experienced PFS longer than 10months. Conclusion Based on tolerability and preliminary evidence of disease control in heavily pretreated CRC patients, NGR-hTNF deserves further evaluation in combination with standard chemotherapy.