CREST: Significant EFS boost seen with sasanlimab plus BCG in NMIBC

Findings from the phase 3 CREST (NCT04165317) study indicate significantly prolonged event-free survival (EFS) with sasanlimab plus BCG compared with BCG alone in patients with high-risk non–muscle invasive bladder cancer (NMIBC).^1,2

Neal D. Shore, MD, FACS

Neal D. Shore, MD, FACS, director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina, presented the data during a plenary session at the 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada.

“The [mechanism of action] for combining BCG with a PD-1 blocker has been well established up-regulating PD, and therefore the synergistic effect of adding a PD blocker. Of note, sasanlimab is delivered subcutaneously, which may be actually very advantageous for certain clinics, both [medical oncology] and [urology].”

The CREST study included 1055 patients with BCG-naïve, high-risk NMIBC that is high-grade Ta and/or carcinoma in situ (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 (OS). Select secondary end points included complete response (CR) in patients with CIS, duration of CR in patients with CIS, safety, and quality of life.

A total of 352 patients were included in arm A and 351 were included in arm C. Median patient age was 67 years in both arms. A total of 280 (79.5%) and 284 (80.9%) patients were male in arms A and C, respectively. A total of 225 (63.9%) and 210 (59.8%) of patients were Caucasian in arms A and C, respectively, and 115 (32.7%) and 126 (35.9%) were Asian.

Regarding disease stage, “55% or higher were T1 patients. Twenty-five percent of this population was CIS, of which 15% was strictly CIS by itself. Looking at the patients and their maintenance of similar rates of BCG, if you look at the discontinuation rates, they're relatively comparable in the combination arm and the BCG arm. What that tells me is that adding sasanlimab did not impact the ability to deliver induction and maintenance BCG,” Shore said.

Shore reported that the risk of experiencing an EFS event was 32% lower in arm A vs arm C (HR=0.68; 95% CI: 0.49-0.94, 1-sided P-value=.0095). Recurrence of high-grade disease was observed in 26 (7.4%) patients in arm A vs 53 (15.1%) patients in arm C. Persistence of CIS was seen in 1 (0.3%) patient in each arm.

EFS was not found to be different between arm B and arm C. “The take-home for this is that BCG maintenance is effective and does matter,” Shore said. He also reported no meaningful difference between treatment arms when it came to interim OS.

Shore also highlighted CR and duration of response in patients with CIS. “In the patients with CIS, the probability of a continued complete response at 36 months was 92% vs 67.7%. I think that's a rather compelling finding,” Shore said.

In terms of adverse events, the safety profile was reported to be consistent with the known safety profile foe each agent.

“We didn't find anything that we hadn't anticipated for this class of therapies, whether it was BCG or a checkpoint inhibitor,” Shore said.

In addition, quality of life was maintained for patients receiving sasanlimab in combination with BCG induction plus maintenance.

“In conclusion, this is the first [of 4 large phase 3 trials evaluating checkpoint blockade in BCG-naïve patients] to show and report here at the AUA 2025…a statistically significant prolongation of EFS with sasanlimab in combination with BCG. [In] patients with CIS the probability of continued CR was greater for the combination—92% vs 68% at 36 months. The safety profile was as expected. I think it's important to recognize the unique subcutaneous administration, and very importantly, that we will need continued collaborative, multi-disciplinary efforts to make sure and optimize shared decision-making for patients who are at risk,” Shore concluded.

In a news release about the results, Megan O’Meara, MD, Interim Chief Development Officer of Pfizer Oncology commented, “Today’s pivotal phase 3 CREST results offer a much-needed therapeutic breakthrough and spotlight sasanlimab as the first immunotherapy combination with BCG to significantly improve outcomes for patients with BCG-naïve, high-risk NMIBC in over three decades. The CREST findings are especially impactful for these patients with early-stage cancer who may benefit the most from innovative treatment regimens, including a subcutaneous immune checkpoint inhibitor, that delay disease recurrence or progression. These results underscore our long-standing commitment to patients with bladder cancer across all stages of the disease. We look forward to working with global regulatory authorities to potentially bring sasanlimab as an important new treatment option to patients with high-risk NMIBC.”^2.

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 April 26, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-significantly-improves-event