Sasanlimab Combo Improves EFS “Across the Board” in BCG-Naïve NMIBC

In a conversation with CancerNetwork®, Thomas Powles, MBBS, MCRP, MD, professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew’s Hospital, Queen Mary University of London, spoke about the efficacy findings from a subgroup analysis of the phase 3 CREST trial (NCT04165317)evaluating sasanlimab and Bacillus Calmette-Guérin (BCG) in BCG-naïve patients with high-risk non–muscle-invasive bladder cancer (NMIBC) that hepresented at the2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Powles began by outlining the study design before delving into the efficacy data, which revealed that the study attained a hazard ratio (HR) of 0.68 (95% CI, 0.49-0.94) for event-free survival (EFS) in the intention-to-treat (ITT) population. Furthermore, he expressed that the subgroup analysis attempted to ascertain benefit in the carcinoma in situ (CIS) subgroup, particularly assessing the role of PD-L1 as a biomarker within this patient group.

Although enrichment could be observed across the entire CIS population, the confidence intervals among the CIS and ITT populations overlapped, with benefit observed among those who had T1 and Ta high-grade disease. Furthermore, PD-L1 was found to be expressed less frequently in the CIS group, indicating that PD-L1 was not predictive of response to sasanlimab.

Powles then emphasized the EFS benefit observed with the combination while suggesting that a 10% to 15% incidence of long-term adverse effects warranted further evaluation of its risk-benefit ratio. He concluded by highlighting the need to identify biomarker-associated responses, remarking that PD-L1 does not appear to be the biomarker in question.

Transcript:

The CREST study is a big randomized phase 3 study [that] includes patients with BCG-naïve, high-risk, [NMIBC]. The intervention is a sasanlimab with BCG. The control arm is BCG alone. The study is positive for [EFS]; that has a [hazard] ratio of 0.68 in the ITT population….We looked at some of the subsets, particularly the CIS subset. We also looked at the role of PD-L1 as a biomarker in this disease.

What, essentially, we showed was some enrichment from that 0.68 to 0.53 associated with the CIS population. We showed quite nice Kaplan-Meier curves that [separate] and stay apart in that subgroup. But, if you look in detail, the confidence intervals of the ITT population are somewhat overlapping with that. And [then] we’ve got other subsets, like T1 and Ta high-grade; they’re also within those confidence intervals. It’s possible to say that while there might be some enrichment, it seems to be working in a broader population as well.

Of course, any subset analysis has the risk of false positive result. At [that] point, we tried to link it with the PD-L1 biomarker because if it were linked with that biomarker, you might say that’s a strong rationale for that working. Actually, we showed that PD-L1 expression was lower in the CIS population, number 1; and number 2, we then tried to see if it was predictive of response to sasanlimab in the ITT population and the CIS T1 or the grade 3 Ta population. We didn’t show biomarker enrichment, particularly in that CIS population.

Overall, it’s fair to say that sasanlimab plus BCG works to prevent events in BCG-naïve [NMIBC], which is great. The drugs were associated with about a 10% to 15% chance of long-term [adverse] effects, and there’s a risk-benefit ratio to be had there. When we look, we can find enrichment in some subgroups, but it’s not complete. It does appear to be working across the board. We do need to identify biomarker-associated responses, but sadly, PD-L1 doesn’t seem to be that.

Reference

Powles TB, Shore ND, Bedke J, 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