Dr Powles on the Role of the CREST Study in Future Clinical Trial Design in BCG-Naive NMIBC

“We’ve tested [sasanlimab] in [NMIBC] in combination with BCG, [and] it showed a reduction in the risk of event-free survival with a hazard ratio of 0.68.”

Thomas Powles, MBBS, MRCP, MD, a professor of genitourinary oncology and the director of the Barts Cancer Centre at St. Bartholomew’s Hospital, highlighted how the phase 3 CREST study (NCT04165317)—evaluating the combination of sasanlimab and BCG in patients with BCG-naive, high-risk, non–muscle-invasive bladder cancer (NMIBC)—could further inform clinical trial designs in NMIBC.

Patients on the trial had BCG-naive, high-risk, T1 or high-grade Ta NMIBC with or without carcinoma in situ, and had not previously received PD-1, PD-L1, PD-L2, or CTLA-4 inhibitors or immunostimulatory agents. Patients (n = 1055) were randomly assigned 1:1:1 to receive sasanlimab plus BCG induction and maintenance (arm A), sasanlimab plus BCG induction (arm B), or BCG induction plus maintenance (arm C).

The novel subcutaneous PD-1 inhibitor sasanlimab has shown clinical activity in urothelial cancer and has been further investigated in the NMIBC paradigm in combination with BCG, Powles began. In the intent-to-treat population in the CREST trial, the event-free survival rates were 84.7% and 82.1% at 24 and 36 months, respectively, in the sasanlimab plus BCG arm (n = 352) compared with 79.9% and 74.8%, respectively, in the BCG induction plus maintenance arm (n = 351; stratified HR, 0.68; 95% CI, 0.49-0.94; 1-sided P = .0095).

Based on this evaluation, investigators have attempted to determine appropriate subgroups of patients who would best benefit from the sasanlimab combination, Powles continued. Although there is a small improvement with the addition of sasanlimab to BCG induction plus maintenance, there’s still more work to be done, he added. The agent has shown activity in other populations of patients; however, whether that activity can be associated with the PD-1 biomarker remains to be seen, he emphasized. There is still work to do, which has been evident through other studies, including the phase 3 POTOMAC trial (NCT03528694), which is evaluating durvalumab (Imfinzi) plus BCG for the treatment of patients with high-risk, BCG-naive NMIBC, Powles concluded.