PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy.

Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility.

Patients with localized MIBC received two doses of nivolumab (480 mg) alone (cohort 1) or with lirilumab (240 mg; cohort 2) prior to RC. Cohorts were enrolled sequentially. The key eligibility criteria were cT2-4aN0-1M0 stage and cisplatin ineligibility/refusal. The primary endpoint was the rate of grade (G) ≥3 treatment-related adverse events (TRAEs) as per Common Terminology Criteria for Adverse Events version 5.0. The key secondary endpoints included the proportion of patients who underwent RC >6 wk after the last dose, CD8+ T-cell density change between pretreatment transurethral resection of bladder tumor (TURBT) and post-treatment RC, ypT0N0, <ypT2N0 rates, 2-yr recurrence-free survival (RFS), and OS.

Among 43 patients enrolled (n = 13, cohort 1; n = 30, cohort 2), 13 and 29 completed intended neoadjuvant therapy, respectively, in cohorts 1 and 2, and 41 underwent RC. The median time from the last dose to RC was 4 wk. The G3 TRAEs occurred in 0% (90% confidence interval [CI] 0-21%) of patients in cohort 1 and 7% (90% CI 1-20%) in cohort 2; all these TRAEs resolved and no G4/5 TRAEs occurred. No patient had delayed RC for >6 wk. In cohorts 1 and 2, ypT0N0 rates for patients with MIBC and RC were 17% and 21%, <ypT2N0 rates were 25% and 32%, 2-yr RFS rates were 73% and 71%, and 2-yr OS rates were 82% and 89%, respectively. CD8+ T-cell density increased significantly from TURBT to RC in cohort 2.

Neoadjuvant nivolumab-based immunotherapy was safe, feasible, and well tolerated in cisplatin-ineligible patients with MIBC. Although ypT0N0 rates were lower than expected, 2-yr survival rates seem to be comparable with those of other neoadjuvant immunotherapy trials. Nivolumab is being evaluated in the CA-017-078 trial (NCT03661320).

For patients with muscle-invasive bladder cancer unable to receive cisplatin-based chemotherapy, treatment with nivolumab without and with lirilumab prior to radical cystectomy was safe, feasible, and well tolerated. Nivolumab-based immunotherapy showed lower pathologic response rates than but similar survival rates to other neoadjuvant immunotherapy trials.

European urology oncology. 2023 Dec 27 [Epub ahead of print]

Petros Grivas, Vadim S Koshkin, Xiangying Chu, Suzanne Cole, Rohit K Jain, Robert Dreicer, Jeremy P Cetnar, Debasish Sundi, Benjamin A Gartrell, Matthew D Galsky, Brianna Woo, Elsa Li-Ning-Tapia, Noah M Hahn, Michael A Carducci

Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA. Electronic address: ., Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA, USA., Dana-Farber Cancer Institute, Boston, MA, USA., University of Texas Southwestern Medical Center, Dallas, TX, USA., H Lee Moffitt Cancer Center, Tampa, FL, USA., University of Virginia Cancer Center, Charlottesville, VA, USA., Oregon Health and Science University, Portland, OR, USA., Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA., Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA., Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA., University of Texas MD Anderson Cancer Center, Houston, TX, USA., Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.