Overall survival and biomarker results of NURE-Combo: A phase 2 study of neoadjuvant nivolumab (NIVO) and nab-paclitaxel (ABX) followed by postsurgical adjuvant NIVO in patients (pts) with muscle-invasive bladder cancer (MIBC).

4594 Background: The first results of NureCombo revealed the combination of NIVO + ABX followed by RC and adjuvant NIVO was active in pts with MIBC (Mercinelli, JCO 2024). We report key secondary endpoints after study completion including adjuvant NIVO for all pts (NCT04876313). Methods: Eligible pts who were cisplatin unfit or declined cisplatin-based treatment had previously untreated MIBC (clinical stage T2-T4a, N0-1, M0), Eastern Cooperative Oncology Group performance status ≤ 1, and predominant ( > 50%) UC histology. Pts received 4 cycles of NIVO 360 mg Q3W + ABX 125 mg/m2 on Day 1 and 8, Q3W, followed by RC and by 13 administrations of adjuvant NIVO 360 mg Q3W. Transcriptome-wide analyses with Decipher Bladder (Veracyte, San Diego, CA) on primary TURBT tissue samples are presented. Continuous scores were dichotomized by median splits. Results: 31 pts were enrolled from 12/2021 to 06/2023, of which 17 (54.8%) had cT3-4 and 14 (45.2%) cT2. N = 2 (6.4%) had cN1 and 15 (48.4%) had a variant histology component. In total, 9 pts (29%) never started the adjuvant NIVO and 15 pts (48.4%) completed it: reason for discontinuation were treatment-related adverse events (TRAE; 5 pts, 16.1%) and relapse (2 pts; 0.6%). Median follow-up was 25 months (IQR: 21-32) and the minimum follow up was 19 months. In total, 7 pts experienced a relapse, 2/7 consisting of an intravesical relapse in those who refused to undergo RC (N = 3). 24-month (24m) event-free survival (EFS) was 73.7% (95%CI 59.6-91.2), corresponding to the 24m relapse-free survival (RFS) post-RC; 24m overall survival (OS) was 89.7% (95%CI 79.3-100; median OS was not reached). There were no additional/late TRAE compared to the initial report. Transcriptome profiles were available for N = 24: Genomic Subtyping Classifier (GSC) stratification revealed ypT0 was highest (50%) in N = 18 Non-luminal (claudin low, basal & infiltrated-luminal) subtypes and lowest (17%) in N = 6 luminal subtype ((p = 0.34). Based on Consensus MIBC classification, none of N = 4 luminal-papillary tumors had a ypT0 response (p = 0.09). Higher Immune190 and higher ESTIMATE-stromal signature trended to better RFS (HR 0.39 & 0.38, respectively). Conclusions: Long-term follow-up results of NureCombo revealed sustained efficacy of ABX-NIVO combination therapy followed by adjuvant NIVO in pts with MIBC. Molecular classification of baseline tumors revealed less favorable pathologic response rates for luminal MIBC. Differences in molecular correlates compared to PURE-01 may be related to different checkpoint inhibition (nivo vs pembro) or due to addition of ABX. Clinical trial information: NCT04876313 .