An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results

Urol Oncol. 2018 Oct;36(10):440-447. doi: 10.1016/j.urolonc.2017.07.005. Epub 2017 Jul 26.

Abstract

Objectives: CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy.

Patients and methods: At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies.

Results: Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%-62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%-78%), CIS ± Ta/T1 50% (33%-67%), and pure Ta/T1 33% (8%-70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment-related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment-related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment-related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment-related AEs.

Conclusions: This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS.

Keywords: BCG unresponsive; Intravesical therapy; Non-muscle invasive bladder cancer; Oncolytic adenovirus.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Administration, Intravesical
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Transitional Cell / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oncolytic Virotherapy / adverse effects
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Antineoplastic Agents