DNA based therapy with diphtheria toxin-a BC-819: A phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer

Ofer N. Gofrit*, Shalva Benjamin, Sarel Halachmi, Ilan Leibovitch, Zohar Dotan, Donald L. Lamm, Nahum Ehrlich, Vladimir Yutkin, Monique Ben-Am, Abraham Hochberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose H19 is a paternally imprinted oncofetal gene expressed in various embryonic tissues and in 85% of bladder tumors but suppressed in the adult healthy bladder. BC-819 is a DNA plasmid that carries the gene for diphtheria toxin-A under regulation of the H19 promoter sequence. We assessed the efficacy and toxicity of intravesical BC-819 instillations to prevent tumor recurrence and ablate a marker lesion in a phase 2b trial. Materials and Methods A total of 47 patients with recurrent, multiple nonmuscle invasive bladder tumors in whom prior intravesical therapy had failed underwent transurethral resection of all except 1 marker tumor. Patients expressing H19 received a 6-week induction course of intravesical BC-819. Patients who achieved a complete response (absent new tumors at 3 months) were given 3 maintenance courses of 3-weekly instillations every 3 months. Results All patients were evaluable for adverse effects and 39 were evaluable for efficacy. Complete tumor ablation was achieved in 33% of patients and in 64% there were no new tumors at 3 months. Median time to recurrence was 11.3 months in all cases but significantly longer (22.1 months) when analyzed by response status at 3 months. Adverse events were mild. The study was limited by the small number of patients. Conclusions BC-819 prevented new tumor growth in two-thirds of the patients and ablated a third of the marker lesions. Prolonged time to recurrence was observed in responding patients. These results along with the good safety profile make BC-819 a potential medication for bladder cancer.

Original languageEnglish
Pages (from-to)1697-1702
Number of pages6
JournalJournal of Urology
Volume191
Issue number6
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • carcinoma
  • diphtheria toxin
  • plasmids
  • urinary bladder
  • urothelium

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