Eugene Cone, MD, discusses recombinant BCG in NMIBC

In this video, Eugene B. Cone, MD, discusses recombinant BCG as an alternative to conventional BCG for patients with non–muscle-invasive bladder cancer (NMIBC), including ongoing clinical evaluation and its potential role in addressing BCG supply challenges. Cone is the co-director of research and a principal physician with Urology of Indiana in Indianapolis, Indiana.

Recombinant BCG is engineered with the goal of producing a more targeted activation of the T-cell pathway than conventional BCG. According to Cone, this approach is intended to maintain or potentially improve antitumor activity while reducing the nonspecific immune activation that can contribute to lower urinary tract symptoms. However, he notes that the hypothesis of improved efficacy has not been established by current data.

Cone also discusses the ongoing ResQ133A-NMIBC trial (NCT06800963), a phase 1/2, open-label study evaluating intravesical recombinant BCG in patients with NMIBC who are eligible to receive TICE BCG. The study is intended to provide data on safety and preliminary efficacy, although it does not have a head-to-head comparator.

“Whether the FDA would give a label based solely off of phase 2 data, or whether they're going to want a head-to-head [trial], especially given that the Tokyo[-172] strain is going to have head-to-head data, remains an open-ended question,” Cone noted.

Recombinant BCG is being evaluated primarily for its ability to expand treatment availability amid ongoing BCG supply challenges in the US. Cone discusses its use in his own practice and notes that some patients have reported less urinary tract irritation compared with prior treatment with TICE BCG, although these observations are anecdotal. He also discusses remaining logistical considerations, including the expanded access process and the potential for an FDA-approved label to simplify access if supporting efficacy data become available.