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


ABSTRACT: 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.

SUBMITTER: Tsujikawa T 

PROVIDER: S-EPMC7727397 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Tsujikawa Takahiro T   Crocenzi Todd T   Durham Jennifer N JN   Sugar Elizabeth A EA   Wu Annie A AA   Onners Beth B   Nauroth Julie M JM   Anders Robert A RA   Fertig Elana J EJ   Laheru Daniel A DA   Reiss Kim K   Vonderheide Robert H RH   Ko Andrew H AH   Tempero Margaret A MA   Fisher George A GA   Considine Michael M   Danilova Ludmila L   Brockstedt Dirk G DG   Coussens Lisa M LM   Jaffee Elizabeth M EM   Le Dung T DT  

Clinical cancer research : an official journal of the American Association for Cancer Research 20200409 14


<h4>Purpose</h4>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 <i>Listeria monocytogenes</i>-expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B).<h4>Patients and methods</h4>Patients with pancreatic adenocarcinoma who received one prior therapy f  ...[more]

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