Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer

Clin Cancer Res. 2020 Jul 15;26(14):3578-3588. doi: 10.1158/1078-0432.CCR-19-3978. Epub 2020 Apr 9.


Purpose: Two studies in previously treated metastatic pancreatic cancer have been completed combining GVAX pancreas vaccine (GM-CSF-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes-expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B).

Patients and methods: Patients with pancreatic adenocarcinoma who received one prior therapy for metastatic disease and RECIST measurable disease were randomized 1:1 to receive treatment on Arm A or Arm B. The primary objective was to compare overall survival (OS) between the arms. Additional objectives included assessment of progression-free survival, safety, tumor responses, CA19-9 responses, and immunologic correlates.

Results: Ninety-three patients were treated (Arm A, 51; Arm B, 42). The median OS in Arms A and B were 5.9 [95% confidence interval (CI), 4.7-8.6] and 6.1 (95% CI, 3.5-7.0) months, respectively, with an HR of 0.86 (95% CI, 0.55-1.34). Objective responses were seen in 3 patients using immune-related response criteria (4%, 2/51, Arm A; 2%, 1/42, Arm B). The grade ≥3 related adverse event rate, whereas higher in Arm A (35.3% vs. 11.9%) was manageable. Changes in the microenvironment, including increase in CD8+ T cells and a decrease in CD68+ myeloid cells, were observed in long-term survivors in Arm A only.

Conclusions: Although the study did not meet its primary endpoint of improvement in OS of Arm A over Arm B, the OS was comparable with standard therapy. Objective responses and immunologic changes in the tumor microenvironment were evident.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Combined Modality Therapy / methods
  • Cyclophosphamide / administration & dosage*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology
  • Mesothelin
  • Nivolumab / administration & dosage*
  • Nivolumab / adverse effects
  • Pancreas / drug effects
  • Pancreas / immunology
  • Pancreas / pathology
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / genetics


  • Cancer Vaccines
  • GPI-Linked Proteins
  • GVAX vaccine
  • Vaccines, Attenuated
  • Nivolumab
  • Cyclophosphamide
  • Mesothelin