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

2. 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

3. 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

4. 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)

5. 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

6. Thank you patrizia.giannatempo@istitutotumori.mi.it