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Wainberg ZA , Hochster HS , Kim EJ , George B , Kaylan A , Chiorean EG , Waterhouse DM , Guiterrez M , Parikh AR , Jain R , Carrizosa DR , Soliman H , Lila T , Reiss DJ , Pierce DW , Bhore R , Banerjee S , Lyons L , Louis CU , Ong TJ , O'Dwyer PJ
Open-Label, Phase 1 Study of Nivolumab Combined With nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer
Clin Cancer Res. 2020 Sep 15;26(18) :4814-4822
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PURPOSE: Assess safety and efficacy of nivolumab plus nab-paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a 2-part, open-label, phase 1 trial. EXPERIMENTAL DESIGN: Fifty chemotherapy-naive patients received nab-paclitaxel 125 mg/m(2) plus gemcitabine 1000 mg/m(2) (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2). Secondary efficacy endpoints were progression-free survival (PFS), overall survival (OS), and response. Assessment of programmed cell death-ligand 1 (PD-L1) expression was an exploratory endpoint; additional biomarkers were assessed post hoc. RESULTS: One DLT (hepatitis) was reported in part 1 among 6 DLT-evaluable patients; 48/50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median (95% CI) PFS/OS was 5.5 (3.25-7.20 months)/9.9 (6.74-12.16 months) months, respectively (median follow-up for OS, 13.6 months [95% CI, 12.06-23.49 months]). Overall response rate (95% CI) was 18% (8.6%-31.4%). Median PFS/OS was 5.5/9.7 months (PD-L1 <5%) and 6.8/11.6 months (PD-L1 >/=5%), respectively. Proportion of peripheral Ki67+ CD8+/CD4+ cells increased significantly from baseline to cycle 3; median peak on-treatment Ki67+ CD8+ T-cell values were higher in responders than in nonresponders. CONCLUSIONS: The safety profile of nivolumab plus nab-paclitaxel and gemcitabine at standard doses in advanced pancreatic cancer was manageable, with no unexpected safety signals. Overall, the clinical results of this study do not support further investigation.
Wainberg, Zev A Hochster, Howard S ORCID: https://orcid.org/0000-0002-9893-1529 Kim, Edward J George, Ben Kaylan, Aparna Chiorean, E Gabriela Waterhouse, David M Guiterrez, Martin Parikh, Aparna R Jain, Rishi Carrizosa, Daniel Ricardo Soliman, Hatem Lila, Thomas Reiss, David J Pierce, Daniel W Bhore, Rafia Banerjee, Sibabrata Lyons, Larry Louis, Chrystal U Ong, Teng J O'Dwyer, Peter J Journal Article United States Clin Cancer Res. 2020 Jun 18. pii: 1078-0432.CCR-20-0099. doi: 10.1158/1078-0432.CCR-20-0099.