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Randomized Phase II study of the safety, efficacy and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR)

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P155

https://doi.org/10.1186/2051-1426-3-S2-P155

  • Published:

Keywords

  • Pancreatic Cancer
  • Cyclophosphamide
  • Pancreatic Cancer Cell
  • Listeria
  • Pancreatic Adenocarcinoma

Background

A heterologous prime-boost vaccination strategy using GVAX pancreas vaccine and CRS-207 is showing promise in patients with pancreatic adenocarcinoma (PDA) (Le, JCO 2015). Furthermore, blockade of the immune checkpoint programmed death-1 (PD-1) is active in some cancers. Combinatorial strategies aimed at priming tumor antigen-specific T cells while simultaneously blocking negative checkpoints may be necessary to improve outcomes in PDA. GVAX is composed of allogeneic pancreatic cancer cells modified to express GM-CSF and induces a broad response against multiple tumor antigens. GVAX is given with low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and is unique in its capacity to stimulate both innate and adaptive immunity by activating T cells and NK cells. Nivolumab is an antibody against PD-1.

Methods

This is a Phase II study comparing CY/GVAX and CRS-207 with or without nivolumab in subjects with PDA who failed only one chemotherapy regimen for metastatic disease. Subjects are randomized in a 1:1 ratio to receive either 2 doses of CY/nivolumab/GVAX and 4 doses of nivolumab/CRS-207 (Arm A) or 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm B). The primary objective is to compare OS between Arms A and B. Secondary/exploratory objectives include: assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with OS, progression-free survival and best overall response.

Authors’ Affiliations

(1)
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
(2)
Providence Cancer Center, Portland, OR, USA
(3)
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
(4)
Departments of Biostatistics and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
(5)
University of Pennsylvania, Baltimore, MD, USA
(6)
Stanford University School of Medicine, Stanford, CA, USA
(7)
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
(8)
Aduro BioTech, Inc., Berkeley, CA, USA
(9)
Aduro Biotech, Berkeley, CA, USA
(10)
Array Biostatistics LLC, Evanston, IL, USA
(11)
Aduro Biotech, Inc., Berkeley, CA, USA

Copyright

© Le et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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