Sasanlimab Plus BCG Displays EFS Benefit Across Key Subgroups in High-Risk Non–Muscle Invasive Bladder Cancer

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Sasanlimab in combination with BCG significantly prolonged event-free survival (EFS) vs BCG monotherapy in patients with high-risk non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) and T1 tumors, according to data from the phase 3 CREST trial (NCT04165317) presented during the 2025 ASCO Annual Meeting.1

Findings from exploratory subgroup analyses of CREST demonstrated that patients with CIS at baseline who received the combination (n = 88) achieved a 36-month EFS rate of 83.0% vs 71.8% in the BCG alone arm (n = 88); the stratified HR for EFS was 0.53 (95% CI, 0.285-0.982). Patients with T1 tumors in the combination arm (n = 204) experienced a 36-month EFS rate of 81.3% vs 72.2% in the BCG alone arm (n = 194); the stratified HR for EFS was 0.63 (95% CI, 0.406-0.963).

“Baseline PD-L1 expression status was not predictive of EFS benefit,” the investigators reported; 17.8% of patients with CIS with and without high-grade Ta/T1 disease were PD-L1 positive, and 26.9% of patients with T1 disease with and without CIS were PD-L1 positive.

“The CREST trial explored a patient population of BCG-naive patients with NMIBC,” Thomas B. Powles, MBBS, MRCP, MD, director of the Barts Cancer Centre at St. Bartholomew’s Hospital in London, United Kingdom, said during the presentation. “The standard of care is BCG. In the 10[55]-patient randomized phase 3 [trial], we added the [subcutaneous] inhibitor sasanlimab to that. Neal Shore [, MD, FACS] beautifully presented the results at [the American Urological Association 2025 Annual Meeting] a few weeks ago. It's a positive study. EFS [HR was] 0.68. Here, we explore some key subgroups, including the CIS subgroup, and we try and link it in with the PD-L1 biology. We showed some enrichment. There was activity across all the groups from an EFS perspective. Sadly, as is often the case, the PD-L1 biomarker may have let us down a little bit.”

As Powles noted, results of CREST were presented during the 2025 AUA Annual Meeting by Neal D. Shore, MD, FACS, the medical director of START Carolinas, formerly the Carolina Urologic Research Center, in Myrtle Beach, South Carolina.2

CREST included 1055 patients with BCG-naive, high-risk NMIBC that is high-grade Ta and/or CIS and had not received prior PD-(L)1, PD-L2, or CTLA-4 inhibitors or immunostimulatory agents. They were randomly assigned 1:1:1 to arm A (sasanlimab plus BCG induction and maintenance), arm B (sasanlimab plus BCG induction), and arm C (BCG induction plus maintenance). The primary end point was EFS for arm A vs arm C. Key secondary end points included EFS in arm B vs arm C, and overall survival. Select secondary end points included complete response (CR) in patients with CIS, duration of CR in patients with CIS, safety, and quality of life.

Safety Findings

Powles also presented safety data from CREST, which was previously reported at AUA 2025. In terms of adverse events (AEs), the safety profile was reported to be consistent with the known safety profile for each agent. Serious treatment-related AEs were observed in 62 (17.7%) patients in arm A and 5 (1.4%) patients in arm C. No patients in arm A or arm C experienced treatment-related AEs leading to death.

“Sasanlimab, in combination with induction and maintenance BCG, prolonged event-free survival compared with BCG alone in patients with BCG-naive, NMIBC. This occurred across subgroups, and there was potential enrichment in that CIS subgroup. CIS was associated with lower PD-L1 levels, and that PD-L1 biomarker was not predictive. BCG maintenance is important, as is the adverse event profile associated with immune checkpoint inhibition. [Subcutaneous] sansanlimab, in combination with BCG, has the potential to change the treatment landscape, particularly in patients with CIS and T1 tumors,” Powles concluded.

References

1. Powles T, Shore N, Galsky M, et al. Sasanlimab in combination with bacillus Calmette-Guérin (BCG) in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): Event-free survival (EFS) subgroup analyses based on disease stage from the CREST study. J Clin Oncol. 2025;43(suppl 17):4517. doi:10.1200/JCO.2025.43.16_suppl.4517
2. 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(5S2):E1. doi:10.1097/01.JU.0001111604.90306.91.01