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

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 -expressing mesothelin). In the current study, we compared Cy/GVAX followed...

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Bibliographic Details
Published in:Clinical cancer research 2020-07, Vol.26 (14), p.3578-3588
Main Authors: Tsujikawa, Takahiro, Crocenzi, Todd, Durham, Jennifer N, Sugar, Elizabeth A, Wu, Annie A, Onners, Beth, Nauroth, Julie M, Anders, Robert A, Fertig, Elana J, Laheru, Daniel A, Reiss, Kim, Vonderheide, Robert H, Ko, Andrew H, Tempero, Margaret A, Fisher, George A, Considine, Michael, Danilova, Ludmila, Brockstedt, Dirk G, Coussens, Lisa M, Jaffee, Elizabeth M, Le, Dung T
Format: Article
Language:English
Subjects:
Cancer Vaccines - administration & dosage
Cancer Vaccines - adverse effects
Combined Modality Therapy - methods
Cyclophosphamide - administration & dosage
GPI-Linked Proteins - genetics
GPI-Linked Proteins - immunology
Humans
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
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Summary: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 -expressing mesothelin). In the current study, we compared Cy/GVAX followed by CRS-207 with (Arm A) or without nivolumab (Arm B). 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. 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. 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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-19-3978