Abraxane-Pembro nei carcinomi uroteliali avanzati A Necchi & P Giannatempo Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Background & Rationale Pembrolizumab (Ab-anti PD-1) FDA-approved in 2nd line UC (Keynote-045) median PFS=2.1 months landmark of 12 months pembrolizumab vs chemo = 16.8% vs 6.2% Nab-paclitaxel: Abraxane Canadian multicenter, single-arm, phase 2 study in second-line UC 48 pts: - ORR 27.7 %, - mPFS=6.0 months - mOS =10.8 months Bellmunt J et al. N Engl J Med 2017 Ko YJ et al. Lancet Oncol 2013

Pembrolizumab 200 mg IV, day 1 NabPaclitaxel 125 mg/m2 IV, day 1,8 PEANUT - An open label, single-arm, phase 2 study of pembrolizumab and nanoparticle albumin-bound paclitaxel in patients with metastatic UC after chemotherapy failure Key eligibility criteria: Histologically-confirmed diagnosis of UC of the bladder or the urothelium ECOG Performance Status of 0 or 1 Measurable disease (RECIST v1.1) Failure of ≤2 cisplatin-based conventional chemotherapy regimens for metastatic disease Neoadjuvant/adjuvant regimens will be counted provided that a relapse occurred within 6 months of the last cycle of chemo Pembrolizumab 200 mg IV, day 1 NabPaclitaxel 125 mg/m2 IV, day 1,8 Every 3 weeks Until loss of clinical benefit, unacceptable toxicity, patient or investigator decision to withdraw, or death N=64

Primary Objective To evaluate whether the combination of pembrolizumab and nab-paclitaxel will be active and will result in an increased activity compared to the available results with the use of both single- agents. Primary Endpoint: Progression-free survival (PFS)

Exploratory Objective Secondary Objective Safety and tolerability Secondary Endpoints: ORR RECIST v1.1; mRECIST OS, G3-4 AE. Exploratory Objective Dynamic biomarkers in both tumor tissue and blood samples: Immunologic assessments Translational analyses on chemo-immunotherapy joint effect: Genomic insights

Thank you patrizia.giannatempo@istitutotumori.mi.it