First 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).
Authors: Chiara Mercinelli, Giuseppe Basile, Daniele Raggi, Antonio Cigliola, Valentina Tateo, Damiano Alfio Patanè, Emanuele Crupi, Tiago Costa de Padua, Maurizio Colecchia, Renzo Colombo, Marco Moschini, Chiara Re, Giulio Avesani, Giorgio Brembilla, Francesco De Cobelli, Alberto Briganti, Dean C. Pavlick, Jeffrey S. Ross, Francesco Montorsi, Andrea Necchi
Journal: Journal of Clinical Oncology (2024)

610 Background: MIBC is a systemic disease with a high risk of recurrence after radical cystectomy (RC), that represents the standard of care (SOC) for cisplatin-ineligible pts. Initial data suggest that ABX is active in combination with pembrolizumab in advanced urothelial carcinoma (UC; PMID:32979512). We report results from a phase 2 trial of NIVO + ABX followed by RC and adjuvant NIVO in pts with MIBC (NCT04876313). Methods: Eligible pts who were cisplatin unfit or declined cisplatin-based treatment had previously untreated MIBC (clinical stage T2-T4a, N0-1, M0, assessed via CT and MRI scan), Eastern Cooperative Oncology Group performance status ≤ 1, and predominant (&gt; 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. The primary endpoint was the pathologic complete response rate (ypT0N0; H0: ≤20% and H1≥ 38% in a 2-stage design: ≥9 ypT0N0 were required in stage 1+2). Secondary endpoints were major pathological response (ypT≤1N0), safety (CTCAE v5.0) and event-free survival (EFS). Tumor biomarkers included comprehensive genomic profiling (CGP) and PD-L1 expression, and circulating tumor DNA monitoring (Signatera). Results: 31 pts were enrolled from 12/2021 to 06/2023; 17 (54.8%) had a cT3-4 stage, 14 (45.2%) a cT2, 2 (6.4%) had N1 stage, 15 (48.4%) had a variant histology component. All 31 pts concluded the neoadjuvant treatment, 29 having pathological response at data cutoff. A total of 4 pts (14.8%) received &lt;4 cycles of neoadjuvant treatment due to treatment-related adverse events (TRAEs). Four patients had G3 TRAEs, including neutropenia (2), asthenia (1), increased AST/ALT (2), neurotoxicity (1) and acute renal failure (1). The median time from start treatment to RC was 4 months (IQR: 3-4). In total, 11 pts (38%; 95%CI 20.3-55.6) achieved an ypT0N0 response and 21 (72%; 95%CI 55.3-88.3) an ypT≤1N0 response. No disease progressions (PD) occurred during neoadjuvant treatment. After a median follow-up of 10.6 months (IQR: 8-16), one pt had a PD: 12-month EFS was 96.4% (95%CI: 89.9-100). Mean tumor mutational burden (TMB) was 12.3 mut/Mb for ypT0N0 responders vs 5.8 mut/Mb for non-responders. All pts with MRI complete response had a ctDNA-negative assay post neoadjuvant NIVO-ABX. Conclusions: The first results from Nure-Combo trial suggest that this novel chemo-immunotherapy combination with NIVO+ABX could be an effective and safe perioperative strategy in pts with MIBC with sustained efficacy post-RC. These results could expand the opportunities of chemotherapy combinations in cisplatin-ineligible pts. Results also strengthen the role of clinical complete response to envision organ-sparing approaches. Clinical trial information: NCT04876313 .