Methods: In an open-label, single-arm, phase 2 trial, pts receive pembro 200 mg intravenously (IV) on D1 and 125 mg/m2 IV nPtx on D1 and D8, every 3 weeks, until disease progression (PD) or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response is evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers include PD-L1 expression with the combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 12/2019, PEANUT study enrolled 63 pts evaluable for the study endpoint: 24% female, median age 69 y (IQR 61-73); 75% had failed 1 prior systemic therapy vs 25% 2 prior therapies; 35% had ECOG-performance status 1; 33% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up of 5 months, 33 pts have relapsed (52%). The median PFS was 5 months (95%CI: 4-not achieved). The confirmed objective response-rate (ORR) was 44.4% (95%CI: 0.34 to 0.55): 19 partial responses and 9 complete responses (14.4%). Grade 3-4 treatment-related adverse events (TRAE) were seen in 14 pts (22%). Most common any-grade TRAE included alopecia (76%), neutropenia (33.3%), and asthenia (33%). Permanent interruption of treatment (nPtx only) was seen in 9 pts (14.2%) due to toxicity. Neither TMB nor CPS were significantly associated with PFS on univariable analyses.

Conclusions: Preliminary results from PEANUT study demonstrated a promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. Updated data, including mature OS, duration of response and biomarkers will be presented.

Citation Format: Patrizia Giannatempo, Daniele Raggi, Elena Farè, Laura Marandino, Marco Bandini, Maurizio Colecchia, Filippo Pederzoli, Giuseppina Calareso, Russell Madison, Francesco Monopoli, Giusy Russo, Roberto Ferrara, Filippo De Braud, Francesco Montorsi, Andrea Necchi. Pembrolizumab and nanoparticle albumin bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT187.