Dr Necchi on Biomarker Data From the SunRISe-4 Trial of Gemcitabine Intravesical System Plus Cetrelimab in MIBC

"What is meaningful in this analysis is the role of MRD assessment by lipid biopsies. There is clearly a double contribution of the 2 components: utDNA towards pCR and ctDNA towards prolonged survival [with gemcitabine intravesical system]."

Andrea Necchi, MD, an associate professor at Vita-Salute Raffaele University and the head of genitourinary medical oncology at IRCCS San Raffaele Hospital and Scientific Institute in Italy, discussed exploratory minimal residual disease (MRD) biomarker data from the phase 2 SunRISe-4 trial (NCT04919512) trial evaluating gemcitabine intravesical system (TAR-200) plus cetrelimab (formerly JNJ-63723283) in patients with muscle-invasive bladder cancer (MIBC) who are scheduled for radical cystectomy and are ineligible/refusing neoadjuvant platinum-based chemotherapy. 

Results from the primary analysis, which were presented during the 2025 ESMO Congress, supported a role for the combination in MIBC, showing a high pathological complete response (pCR) rate of 38% (95% CI, 28%-49%) in cohort 1 (n = 88) and 1-year recurrence-free survival (RFS) rate of 77% (95% CI, 67%-85%) in this group (n = 35). In contrast, the pCR rate was 28% (95% CI, 16%-44%) with cetrelimab monotherapy (n = 46). The 1-year RFS was 64% (95% CI, 47%-77%) in this cohort (n = 20).

Additional analyses focused on MRD assessment using circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) liquid biopsies, supporting their investigation as predictive biomarkers for residual disease after neoadjuvant therapy in MIBC. Necchi highlighted the meaningful role of MRD assessment.

Baseline utDNA MRD was positive in 82.1% of patients (n = 55) but dropped to 52.3% after treatment (n = 34). Of note, utDNA MRD assessed at week 12 was strongly associated with pCR regardless of treatment, Necchi reported. In total, 81.5% of patients who achieved pCR were utDNA MRD negative at week 12 vs 21.2% who did not achieve a pCR (Fisher’s test P = 5.4 x 10-6).

Conversely, ctDNA confirmed an association with RFS, whether assessed at baseline (n = 44; HR, 4.42; 95% CI, 0.91-21.3; P = .04) or week 12 (n = 44; HR, 4.66; 95% CI, 1.24-17.4; P = .01). However, week 12 ctDNA MRD status and ctDNA clearance were not significantly associated with pCR (P = .12 and .15, respectively). Necchi emphasized that these two components both contributed to improved outcomes, with utDNA MRD being associated with pCRs and ctDNA MRD being predictive of longer survival outcomes. Given these efficacy, biomarker, and safety data, Necchi concluded that this combination warrants further pursuit.

Disclosures: Necchi disclosed financial interests, institutional, and research funding from Merck; financial interests, institutional funding, and research grants from AstraZeneca, Bristol-Myers Squib, Gilead, Ipsen; financial interests, institutional funding, roles as a consultant/advisor with Astellas, AstraZeneca, Bristol-Myers Squibb, Catalym, Gilead, Johnson & Johnson, Samsung Bioepis, Bicycle Therapeutics, Merck; financial interests, institutional funding and a leadership role with the Global Society of Rare Genitourinary Tumors (GSRGT); financial interests, institutional funding, and a role as an associate editor for the Journal of Clinical Oncology.

Disclosures: Necchi received grants or institutional research funding from AstraZeneca, Bristol Myers Squibb (BMS), Gilead, Ipsen, and Merck. He received consulting or advisory fees from Astellas, AstraZeneca, BMS, Catalym, Gilead, Johnson & Johnson, Samsung Bioepis, Bicycle Therapeutics, and Merck. He also serves in a leadership role for the Global Society of Rare Genitourinary Tumors, and as an associate editor for the Journal of Clinical Oncology.

Reference

Necchi A, Guerrero-Ramos F, Crispen PL, et al. Neoadjuvant gemcitabine intravesical system (TAR-200) + cetrelimab or cetrelimab alone in patients with muscle-invasive bladder cancer: SunRISe-4 primary analysis and biomarker results. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA112.