Dr Lotan on Ongoing Research With Novel Agents in BCG-Unresponsive NMIBC

Yair Lotan, MD, professor, urology, chief, urologic oncology, Jane and John Justin Distinguished Chair in Urology, UT Southwestern Harold C. Simmons Comprehensive Cancer Center; medical director, Urology Clinic, UT Southwestern and Parkland Health and Hospital System, discusses ongoing research with novel agents in patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC).

Several agents are under investigation in clinical trials in this patient population, many of which may receive FDA approval in the future. First, the phase 2b SunRISe-1 trial (NCT04640623) is evaluating TAR-200, which uses a novel drug delivery system that facilitates the sustained release of gemcitabine directly into the bladder. The device is inserted and removed cytoscopically and is replaced every 3 weeks during the first 6 months of treatment. In data presented during the 2024 ESMO Congress, the complete response (CR) rate was 83.5% (95% CI, 74%-91%) with TAR-200 monotherapy, and the estimated 12-month duration of response rate was 65.7% (95% CI, 45.2%-80.1%).

In cohort A of the single-arm, phase 2 KEYNOTE-057 trial (NCT02625961), at 3 months, the CR rate was 41% with pembrolizumab monotherapy in patients with high-risk disease without carcinoma in situ. Regarding a phase 3 trial (NCT02773849) investigating nadofaragene firadenovec-vncg (Adstiladrin), at 3 months, the CR rate with this agent was 53.4%. At 1 year, the CR rate was 45.5%. Additionally, in cohort A of the phase 2/3 QUILT-3.032 trial (NCT03022825), at a median follow-up of 23.9 months, the rate of CR at any time with nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG was 71% (95% CI, 59.6%-80.3%). Finally, for those enrolled in the phase 3 BOND-003 trial (NCT04452591), the rate of CR at any time with cretostimogene grenadenorepvec monotherapy was 75.2% (95% CI, 65%-83%), and responses were durable, Lotan explains.

Lastly, the phase 1/2 LEGEND trial (NCT04752722) is evaluating the intravesical therapy EG-70 in patients with high-risk, BCG-unresponsive NMIBC. The phase 1 portion of this trial is complete, and the phase 2 portion is ongoing, he notes. Early data from this trial have shown promising responses with EG-70, and response durability data will help determine whether this agent should join the NMIBC treatment paradigm, Lotan concludes.