Faculty Collaboration Database

Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer. Clin Cancer Res 2020 Sep 15;26(18):4814-4822

Date

06/20/2020

Pubmed ID

32554514

DOI

10.1158/1078-0432.CCR-20-0099

Scopus ID

2-s2.0-85096537917 (requires institutional sign-in at Scopus site)   78 Citations

Abstract

PURPOSE: Assess safety and efficacy of nivolumab plus nab-paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial.

PATIENTS AND METHODS: Fifty chemotherapy-naive patients received nab-paclitaxel 125 mg/m² plus gemcitabine 1,000 mg/m² (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 six DLT-evaluable patients; 48 of 50 patients experienced grade 3/4 TEAEs and 18 discontinued treatment due to TEAEs. One grade 5 TEAE (respiratory failure) was reported. Median [95% confidence interval (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.

Author List

Wainberg ZA, Hochster HS, Kim EJ, George B, Kaylan A, Chiorean EG, Waterhouse DM, Guiterrez M, Parikh A, Jain R, Carrizosa DR, Soliman HH, Lila T, Reiss DJ, Pierce DW, Bhore R, Banerjee S, Lyons L, Louis CU, Ong TJ, O'Dwyer PJ

Author

Ben George MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Albumins
Antineoplastic Combined Chemotherapy Protocols
Deoxycytidine
Female
Humans
Male
Middle Aged
Neoplasm Staging
Paclitaxel
Pancreatic Neoplasms