SunRISe-4: Neoadjuvant TAR-200/cetrelimab is linked with strong pCR, pOR in MIBC

Neoadjuvant treatment of muscle-invasive bladder cancer (MIBC) with TAR-200 plus cetrelimab was associated with strong pathologic complete response (pCR) and pathologic overall response (pOR) rates, according to data from the phase 2 SunRISe-4 study (NCT04919512).

The findings were presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain, by Andrea Necchi, MD.¹

Andrea Necchi, MD

“There is a high unmet need for more effective and safe [treatment] to provide in the neoadjuvant setting, in particular for patients for whom chemotherapy is not an option,” said Necchi, an associate professor of oncology at the Vita-Salute San Raffaele University and the director of GU medical oncology at San Raffaele Hospital in Milan, Italy.

According to the authors, “TAR-200 is a gemcitabine intravesical releasing system designed to provide sustained gemcitabine within the bladder.” The device is placed using urinary placement catheter during a 2- to 3-minute procedure performed in the office setting.

Previously reported phase 1 researched demonstrated clinical activity for TAR-200 in patients with MIBC.^2,3

SunRISe-4 is ongoing phase 2 randomized study evaluating the efficacy and safety of neoadjuvant TAR-200 plus cetrelimab or cetrelimab monotherapy in patients with MIBC who are scheduled for radical cystectomy and who are ineligible for or refuse neoadjuvant chemotherapy.

The patient population consisted of adult patients who had histologically confirmed cT2-T4a N0M0 MIBC, predominant urothelial carcinoma histology, ECOG performance status of 0-1, were ineligible for or refused neoadjuvant chemotherapy, and were scheduled to receive radical cystectomy. Patients were stratified by visible residual disease at transurethral resection of bladder tumor—complete vs incomplete, and tumor stage at MIBC diagnosis: cT2 vs cT3-4a. Patients were randomly assigned 5:3 to either TAR-200 plus cetrelimab (cohort 1) or cetrelimab alone (cohort 2) followed by radical cystectomy.

The primary end point was pCR (ypT0N0). Secondary end points included recurrence-free survival and safety, and exploratory end points included pOR (≤ypT0N0), overall survival (OS), time to symptomatic progression, quality of life according to FACT-BI, pharmacokinetics, and biomarker analysis.

“The study aimed to determine to the contribution of the 2 components toward the pathological response. It’s important to underscore the fact that it’s not a comparative study. The study [does not] aim to compare the 2 arms, but is just [meant] to provide the summary of the efficacy and safety data in either arm,” Necchi said.

During his presentation, Necchi provided results of interim analysis 2, at which point approximately 80 total patients had undergone radical cystectomy.

Reviewing baseline characteristics, Necchi reported that 31 (39/2%) of patients in cohort 1 were ineligible for neoadjuvant chemotherapy, and 15 (36.6%) of patients in cohort 2 were ineligible for neoadjuvant chemotherapy. In addition, 16 (20.3%) patients in cohort 1 and 6 (14.6%) patients in cohort 2 had residual disease at the start of treatment, and 16 (20.3%) patients in cohort 1 and 11 (26.8%) patients in cohort 2 had urothelial carcinoma with variant histology.

Necchi reported that pCR was 42% (95% CI, 28-56) in cohort 1 and 23% (95% CI, 10-41) in cohort 2. pOR was 60% in cohort 1 (95% CI, 46-74) and 36% (95% CI, 19-55) in cohort 2.

In cohort 1, pCR was 27% (95% CI, 6-61) in patients who received 1 to 2 doses of TAR-200, 30% (95% CI, 7-65) in those who received 3 doses, and 50% (95% CI, 32-68) in those who received 4 doses.

Regarding treatment-related adverse events (TRAEs), 57 (72.2%) patients in cohort 1 and 18 (43.9%) patients in cohort 1 experienced at least 1 TRAE. Immune-related AEs of grade 3 or higher occurred in 6.3% of patients in cohort 1 and 4.9% of patients in cohort 2. Median time to radical cystectomy was 13.7 weeks in cohort 1 and 12.6 weeks in cohort 2.

“SunRISe-4 demonstrated for the first time a benefit from the combination of an intravesical therapy with TAR-200 with a systemic immune checkpoint inhibitor in patients with MIBC,” Necchi said in his concluding remarks.

REFERENCES

1. 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 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA84. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA84.html.pdf

2. Daneshmand S, Brummelhuis ISG, Pohar KS, et al. The safety, tolerability, and efficacy of a neoadjuvant gemcitabine intravesical drug delivery system (TAR-200) in muscle-invasive bladder cancer patients: a phase I trial. Urol Oncol. 2022;40(7):344.e1-344.e9. doi:10.1016/j.urolonc.2022.02.009

3. Tyson MD, Morris D, Palou J, et al. Safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who refused or were unfit for curative-intent therapy: a phase 1 study. J Urol. 2023;209(5):890-900. doi:10.1097/JU.0000000000003195