Abstracts

Clinical and pathological response in a Phase II trial (SGN-00101-9902) of HspE7 in high grade anal dysplasia

Abstract presented at HPV 2000 - 18th International Papillomavirus Conference (Barcelona, Spain, July 23-28, 2000)

Goldstone S.E. (1); Thompson J.A. (2); Neefe J.R. (3)

1) Mt. Sinai School of Medicine, New York, NY, USA,
2) Impath, Los Angeles, CA, USA and
3) Stressgen Biotechnologies, Inc., Collegeville, PA, USA

Human papillomavirus (HPV) causes anal dysplasia and probably anal cancer. For treatment of HPV, we have constructed a fusion protein, HspE7, consisting of the heat shock protein Hsp65 from M. bovis BCG linked to the Rb-blocking E7 protein from the oncogenic HPV type 16. A randomized, double blind, placebo-controlled trial (SGN-00101-9901) of 3 monthly subcutaneous doses of HspE7, 100 µg, was conducted in patients with biopsy-proven anal high grade squamous intraepithelial lesions (HSIL). Patients with persistent HSIL in biopsy specimens taken 1 month after completing 3 injections were permitted to cross over to an open label trial (9902) of 3 doses of HspE7, 500 µg. The first 8 consecutive patients in this cross-over study were enrolled at a single site.

This report represents the investigator's analysis of the course of these patients. Seven men and 1 woman crossed to 9902. After 3 injections of HspE7, all had evidence of clinical response determined colposcopically, and the physician's global assessment of clinical benefit improved by 65% to 95%. For all 8, the surgical procedure that would have been recommended for clearance of lesions became less extensive and/or less invasive. At baseline, 5/8 would have required surgery under general anesthesia and 3/8 would have required an office ablation such as laser surgery. After treatment, 1/8 would have required no procedure and 5/8 would have required topical treatment only one still would have required surgery under general anesthesia but as a much less extensive procedure. Serial biopsies were taken from all patients. Baseline showed HSIL in all 8. One month after the third injection, dysplasia was improved in all patients: 1 had no dysplasia, 2 had LSIL, and 5 had less extensive (focal) or less severe dysplasia than at baseline.

These preliminary data suggest that HspE7 is active in anal dysplasia. Further follow up at the 6-month observation point may reveal additional improvement without additional treatment. A phase III randomized, double blind, placebo-controlled study (SGN-00101-0001) is planned to reproduce these observations in rigorous fashion.