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

Takahiro Tsujikawa, Todd Crocenzi, Jennifer N. Durham, Elizabeth A. Sugar, Annie A. Wu, Beth Onners, Julie M. Nauroth, Robert A. Anders, Elana J. Fertig, Daniel A. Laheru, Kim Reiss, Robert H. Vonderheide, Andrew H. Ko, Margaret A. Tempero, George A. Fisher, Michael Considine, Ludmila Danilova, Dirk G. Brockstedt, Lisa M. Coussens, Elizabeth M. JaffeeDung T. Le

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77 Scopus citations


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 CD8þ T cells and a decrease in CD68þ 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.

Original languageEnglish (US)
Pages (from-to)3578-3588
Number of pages11
JournalClinical Cancer Research
Issue number14
StatePublished - Jul 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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