Open-label, Phase I Study of Nivolumab Combined with nab-Paclitaxel plus Gemcitabine in Advanced Pancreatic Cancer

Zev A. Wainberg, Howard S. Hochster, Edward J. Kim, Ben George, Aparna Kaylan, E. Gabriela Chiorean, David M. Waterhouse, Martin Guiterrez, Aparna Parikh, Rishi Jain, Daniel Ricardo Carrizosa, Hatem H. Soliman, Thomas Lila, David J. Reiss, Daniel W. Pierce, Rafia Bhore, Sibabrata Banerjee, Larry Lyons, Chrystal U. Louis, Teng Jin OngPeter J. O’Dwyer

Research output: Contribution to journalArticlepeer-review

15 Scopus 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 Ki67þ CD8þ/CD4þ cells increased significantly from baseline to cycle 3; median peak on-treatment Ki67þ CD8þ 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.

Original languageEnglish (US)
Pages (from-to)4814-4822
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number18
DOIs
StatePublished - Sep 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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