A phase I clinical trial demonstrates that nfP2X7 -targeted antibodies provide a novel, safe and tolerable topical therapy for basal cell carcinoma.

ABSTRACT

BACKGROUND: Expression of P2X7 , an ATP-gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X7 (termed nfP2X7 ), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers. OBJECTIVES: To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for basal cell carcinoma (BCC). METHODS: An open-label, phase I clinical trial was undertaken at three dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X7 antibodies (BIL010t) to primary BCC lesions twice daily for 28 days. Twenty-one patients with primary BCC lesions at least 0·5 cm2 in area and less than 2·0 cm in diameter were enrolled. The primary end points were safety, tolerability and pharmacokinetics. Change in lesion size after treatment was determined and histology was performed on pretreatment and end-of-treatment (EOT) biopsies. RESULTS: Compliance was very high, with treatment being well tolerated. The most common adverse events were treatment site erythema, pruritus, dryness and pain. There was no evidence of systemic penetration of the sheep antibody. Lesions were measured prior to and after 28 days of treatment, with 65% of patients showing a reduction in lesion area, 20% showing no change and 15% showing an increase. Histopathology of post-treatment excision of lesion sites showed eight patients with stable disease, nine with partial response and three with complete response. CONCLUSIONS: Antibodies against nfP2X7 (BIL010t) provide a novel, safe and well-tolerated treatment for BCC.