Antiangiogenic metargidin
peptide (
AMEP) is a novel
anticancer agent exerting antiproliferative and antiangiogenic effects by binding to αvβ3 and α5β1
integrins. Electrotransfer designates the use of electric pulses (electroporation) to transfer plasmid
DNA into tissues. This first-in-man phase I study investigated safety and tolerability of intratumoral plasmid
AMEP electrotransfer into cutaneous metastatic
melanoma. Secondary objectives were efficacy and pharmacokinetics. Five patients with disseminated
melanoma without further treatment options were treated at two dose levels (1 and 2 mg
DNA). In each patient, two cutaneous lesions were identified (one treated and one control). At day 1 and day 8, plasmid
AMEP was injected intratumorally followed by electrotransfer. Patients were monitored weekly until day 29, and at day 64. Local efficacy was assessed at day 29 by direct measurement, and posttreatment biopsies for
AMEP mRNA levels were evaluated by
reverse transcriptase quantitative polymerase chain reaction. Plasmid copy number in blood and urine was determined by quantitative polymerase chain reaction. Minimal systemic toxicity was observed, including transient
fever and transitory increase in
C-reactive protein. No related serious adverse events occurred. Plasmid
AMEP was detected in plasma but not in urine.
AMEP mRNA was found in three of five treated lesions and none of the control lesions. At day 29, all five treated lesions were stable in diameter, whereas four of five control lesions increased more than 20%. No response occurred in distant lesions. This first-in-man study on electrotransfer of plasmid
AMEP into cutaneous
melanoma shows that the procedure and
drug are safe and that local transfection was obtained.