Andrea Necchi, MD, Vita-Salute San Raffaele University, Milan, Italy, discusses results from the SunRISe-4 study which assessed TAR-200 plus cetrelimab in a cohort of patients with muscle-invasive bladder cancer who either refused or were ineligible for cisplatin-based chemotherapy. The results found that the addition of TAR-200 improved pathological complete response rate and the rate of patients pathological downstaged to non-muscle invasive disease.

Dr Necchi presented these results at the 2024 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Transcript: 

Hello, I'm Andrea Necchi. I'm an associate professor of oncology at Vita-Salute San Raffaele University in Milan, Italy. It's a pleasure to be here today summarizing the data that we are presenting here at the congress, at the ESMO meeting, regarding the SunRISe-4 study. 

The SunRISe-4 study is a randomized phase 2 study, testing the combination of TAR-200 and cetrelimab or cetrelimab monotherapy in patients with muscle-invasive bladder cancer who are unsuited for or refuse neoadjuvant cisplatin-based chemotherapy. 

TAR-200 is a gemcitabine-releasing system that is put into the bladder through a catheter. It's a silicone tube that is releasing gemcitabine through an osmotic system into the bladder and it has already provided data in non-muscle invasive disease, and preliminary data in activity and safety in muscle-invasive disease. The study combined TAR-200 with the checkpoint inhibitor cetrelimab in these patients in the experimental cohort, in the combination therapy cohort. The primary end point of the study was pathological complete response [pCR] and the major summary of the data with regards to the pathological response, suggesting that the pCR rate for the combination therapy was 42% in the efficacy evaluable population, all the T2/T4 patients included, and the pathological downstaging to non-muscle invasive disease was 60%. [The] same data in the cetrelimab monotherapy cohort were 23% and 36%. 

In particular, when we look at the data for the primary end point in subgroups of the patients, and key subgroups represented by patients with T2 vs T3/T4 or results by completeness of prior TURBT, the results were quite promising. In clinical T2 patients, the pathological complete response rate [rose] to 48%, so almost at 50%, and the pathological downstaging to non-muscle invasive disease [rose] up 68%, so quite promising enrichment. 

Another important feature is that these results were consistent regardless of the completeness of the TURBT, so patients starting therapy with a visible, residual disease after the previous resection benefited the same from treatment as the patients with a complete TURBT. 

Another important point is the association was evident between TAR-200 exposure and the pathological complete response. Patients, the majority who were able to complete the 4 courses of neoadjuvant therapy, neoadjuvant TAR-200 and cetrelimab, benefited with a pCR rate that reached 50% in the very high pathological downstaging rate, suggesting that there is a learning curve that is needed by urologists in order to optimize the management of this device and of this treatment. 

Lastly, but a not less important point is related to safety. Combination therapy was characterized by very low rate of grade 3/4 treatment-related adverse events. The immune-related adverse events were in the range of 10%, very few patients discontinued treatment due to treatment-related adverse events, we had just 1 treatment-related death in the cetrelimab monotherapy cohort. 

Overall the combination therapy was really quite promising, and the combination of the safety and the preliminary activity of this combination therapy sets this opportunity as a potential new option for the patients if the results will be confirmed by the conclusive results from the SunRISe-4 study and by further studies. 

SunRISe-4 is a part of the platform study of SunRISe studies that are investigating TAR-200 alone or in combination with immune therapy in various disease stages, including non-muscle invasive disease and muscle-invasive disease, and the results from SunRISe-4 suggested that there could be an opportunity to get important responses in the primary tumor, envisioning the potential future for next strategies. Next level strategies aim to differentiate a little bit from the classical neoadjuvant studies and the radical removal of the bladder that may be potentially envisioning new therapies that will provide a bladder-sparing approach.

Source: 

Necchi A, Guerrero-Ramos F, Crispen PL, et al. TAR-200 plus cetrelimab (CET) or CET alone as neoadjuvant therapy in patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for or refuse neoadjuvant cisplatin-based chemotherapy (NAC): Interim analysis of SunRISe-4 (SR-4). Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA84