Dr Necchi on TAR-200 & Cetrelimab in Bladder Cancer

Based on primary analysis data from the phase 2 SunRISe-4 study, the combination of the neoadjuvant gemcitabine intravesical system (TAR-200; Inlexzo) plus the checkpoint inhibitor cetrelimab demonstrated high pathologic complete response (pCR) and recurrence-free survival (RFS) rates in patients with muscle-invasive bladder cancer (MIBC). In an interview, Andrea Necchi, MD, Università Vita-Salute San Raffaele, discusses the data from SunRISe-4 presented at the 2025 ESMO Congress.

The findings are particularly relevant for patients scheduled for radical cystectomy who are ineligible for or refuse standard cisplatin-based chemotherapy. For these patients, the typical alternative is immediate surgery, which has a pCR rate of only 10% to 15%.

The study randomized patients into two groups. Cohort 1 (n = 88) received the TAR-200 and cetrelimab combination, while cohort 2 (n = 46) received cetrelimab monotherapy. The primary end point was the pCR rate.

Results showed a significant benefit for the combination therapy. Cohort 1 achieved a pCR rate of 38% compared with 28% in the monotherapy cohort. The pathologic overall response (pOR) rate was also higher in the combination arm, at 53% versus 44%. Furthermore, the 12-month recurrence-free survival rate was 77% for the combination group, notably higher than the 64% rate observed in the cetrelimab-only group.

Exploratory analyses also suggested that urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) minimal residual disease (MRD) status could serve as predictive biomarkers. A utDNA MRD-negative status at 12 weeks and utDNA clearance from baseline were both strongly associated with achieving a pCR. Moreover, ctDNA MRD-negative status at baseline and at 12 weeks correlated with longer RFS.

Researchers concluded that the promising data support further investigation of the TAR-200 plus cetrelimab combination as an effective neoadjuvant treatment option for this specific MIBC patient population.