Ongoing clinical trials of BCG/ICI combinations in BCG-naïve NMIBC

In BCG-naïve non–muscle invasive bladder cancer (NMIBC), emerging options are largely focused on combining BCG with immune checkpoint inhibitors (ICIs). By targeting the PD-1/PD-L1 pathway, it is expected that these regimens may overcome the mechanisms of resistance that challenge treatment with BCG monotherapy.

Several of these combinations are currently under phase 3 study, with the first trial, CREST, reading out earlier this year. Data from several other key trials, such as POTOMAC and ALBAN, are soon expected.

These regimens could redefine the treatment landscape for BCG-naïve NMIBC. To highlight this shift, we’ve outlined the pivotal trials investigating BCG/ICI combinations that are poised to shape the future of care in this setting.

Trial: CREST

Regimen: Sasanlimab plus BCG

The phase 3 CREST trial (NCT04165317) is evaluating the combination of sasanlimab plus BCG in patients with high-risk BCG-naïve NMIBC. Initial data from the trial read out during a plenary session at the 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada,¹ marking sasanlimab as the first immunotherapy in combination with BCG to show improved outcomes in this patient population.

In total, the trial enrolled 1055 patients who were randomly assigned 1:1:1 to arm A (sasanlimab plus BCG induction and maintenance), arm B (sasanlimab plus BCG induction), or arm C (BCG induction plus maintenance).

Overall, data showed that the combination of sasanlimab plus BCG (induction and maintenance) significantly improved event-free survival (EFS) vs BCG alone (HR, 0.68; 95% CI, 0.49 to 0.94; 2-sided P = .019). Specifically, the probability of being event-free at 36 months was 82.1% (95% CI, 77.4 to 85.9) in the combination arm vs 74.8% (95% CI, 69.7 to 79.2) in the BCG monotherapy arm. At the time of data report, the median EFS had not been reached.

Data showed no statistically significant difference in EFS between arm B (sasanlimab plus BCG induction) vs arm C (BCG induction plus maintenance), suggesting the importance of BCG maintenance in this setting.

In a news release on these findings, Pfizer confirmed that they had shared these data with global health authorities to support potential regulatory filings for the combination.²

Trials: POTOMAC and PATAPSCO

Regimen: Durvalumab plus BCG

Another BCG/ICI regimen, BCG plus durvalumab (Imfinzi), is being explored in the POTOMAC (international; NCT03528694) and PATAPSCO (US; NCT05943106) trials.

Although full data from those studies are not yet available, topline results from the POTOMAC trial were shared in May 2025 by AstraZeneca.³ Overall, the company reported that the addition of durvalumab to BCG induction plus maintenance led to a statistically significant improvement in disease-free survival. Full results from the trial are expected to be shared at the upcoming European Society of Medical Oncology (ESMO) Congress in Berlin, Germany.

In a recent interview with Urology Times®, Suzanne B. Merrill, MD, FACS, suggested that—based on what was seen in the CREST trial—key data points from POTOMAC will be on the impact of durvalumab on disease progression, as well as the safety profile of the agent.

Trial: ALBAN

Regimen: Atezolizumab plus BCG

The phase 3 ALBAN trial (NCT03799835), also expected to read out at this year’s ESMO Congress, is exploring the combination of atezolizumab (Tecentriq) plus BCG in patients with high-risk BCG-naïve NMIBC. In total, the trial enrolled 517 patients across 45 clinical trial sites in Europe.⁴

Those enrolled in the study were randomly assigned 1:1 to receive BCG alone (arm A) or BCG in combination with atezolizumab (arm B). Patients are stratified by center and carcinoma in situ.

The primary end point for the study is EFS, with key secondary end points including high-grade recurrence-free survival, progression-free survival, overall survival, and safety. Final completion of the study is expected in October 2028.

REFERENCES

1. Shore ND, Powles T, Bedke J, et al. Sasanlimab in combination with Bacillus Calmette-Guérin improves event-free survival versus Bacillus Calmette Guérin as standard of care in high-risk non-muscle invasive bladder cancer: Phase 3 CREST study results. J Urol. 2025;213(5S).

2. Pfizer’s sasanlimab combination significantly improves event-free survival in BCG-naïve, high-risk non-muscle invasive bladder cancer. News release. Pfizer. April 26, 2025. Accessed September 25, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-significantly-improves-event

3. Patients lived significantly longer without high-risk disease recurrence or progression after one year of Imfinzi treatment plus Bacillus Calmette-Guérin (BCG) induction and maintenance therapy vs. BCG alone. News release. AstraZeneca. May 9, 2025. Accessed September 25, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-improved-dfs-in-early-bladder-cancer.html

4. Atezolizumab plus one-year BCG bladder instillation in BCG-naive high-risk non-muscle invasive bladder cancer patients (ALBAN). ClinicalTrials.gov. Last updated December 11, 2024. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT03799835