Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH(2)), a beta integrin antagonist, in patients with solid tumours
To assess the toxicity, pharmacological, and biological characteristics of ATN-161—a five-amino-acid peptide derived from fibronectin’s synergy region—adult patients with advanced solid tumors were enrolled across eight sequential dose cohorts (0.1–16 mg/kg). ATN-161 was administered as a 10-minute intravenous infusion three times per week. Pharmacokinetic (PK) analyses of blood and urine were conducted over a 7-hour period on Day 1.
A total of 26 patients received between 1 and 14 treatment cycles (each cycle lasting 4 weeks), with 86 cycles administered in total. No dose-limiting toxicities were observed. At doses above 0.5 mg/kg, ATN-161 exhibited dose-independent clearance and volume of distribution, while reduced clearance at 8.0 and 16.0 mg/kg suggested saturable PKs. Dose escalation was stopped at 16 mg/kg when drug exposure (AUC) exceeded levels associated with efficacy in preclinical models.
Although no objective tumor responses were reported, six patients maintained stable disease for more than four cycles (>112 days), and three patients continued treatment for 10 or more cycles (≥280 days). ATN-161 was well tolerated at all dose levels, and approximately one-third of patients experienced prolonged stable disease. These results support further investigation of ATN-161 as a potential antiangiogenic and antimetastatic therapy,Ac-PHSCN-NH2 either alone or in combination with chemotherapy.