Several novel agents are showing promise in clinical trials for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC), offering potential new treatment options for this challenging patient population. These agents are under investigation and may receive FDA approval in the future.
TAR-200
The phase 2b SunRISe-1 trial (NCT04640623) is evaluating TAR-200, 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. Data presented at the 2024 ESMO Congress showed a complete response (CR) rate of 83.5% (95% CI, 74%-91%) with TAR-200 monotherapy. The estimated 12-month duration of response rate was 65.7% (95% CI, 45.2%-80.1%).
Pembrolizumab
In cohort A of the single-arm, phase 2 KEYNOTE-057 trial (NCT02625961), pembrolizumab monotherapy achieved a 41% CR rate at 3 months in patients with high-risk disease without carcinoma in situ.
Nadofaragene Firadenovec-vncg
A phase 3 trial (NCT02773849) investigating nadofaragene firadenovec-vncg (Adstiladrin) showed a CR rate of 53.4% at 3 months. At 1 year, the CR rate was 45.5%.
Nogapendekin Alfa Inbakicept-pmln
In cohort A of the phase 2/3 QUILT-3.032 trial (NCT03022825), nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG resulted in a CR rate of 71% (95% CI, 59.6%-80.3%) at any time, with a median follow-up of 23.9 months.
Cretostimogene Grenadenorepvec
For patients enrolled in the phase 3 BOND-003 trial (NCT04452591), cretostimogene grenadenorepvec monotherapy achieved a CR rate of 75.2% (95% CI, 65%-83%) at any time, with durable responses.
EG-70
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. 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.
