Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study)

Dung Le, Vincent J. Picozzi, Andrew H. Ko, Zev A. Wainberg, Hedy Kindler, Andrea Wang-Gillam, Paul Oberstein, Michael A. Morse, Herbert J. Zeh, Colin Weekes, Tony Reid, Erkut Borazanci, Todd Crocenzi, Noelle K. LoConte, Benjamin Musher, Daniel Laheru, Aimee Murphy, Chan Whiting, Nitya Nair, Amanda EnstromSandy Ferber, Dirk G. Brockstedt, Elizabeth Jaffee

Research output: Contribution to journalArticle

Abstract

Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.

Original languageEnglish (US)
Pages (from-to)5493-5502
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number18
DOIs
StatePublished - Sep 15 2019

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Multicenter Studies
Pancreas
Adenocarcinoma
Drug Therapy
Cyclophosphamide
Survival
gemcitabine
Pancreatic Neoplasms
Therapeutics
Confidence Intervals
Chills
Listeria monocytogenes
Granulocyte-Macrophage Colony-Stimulating Factor
Nausea
Fatigue
Neoplasms
Fever
Physicians
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study). / Le, Dung; Picozzi, Vincent J.; Ko, Andrew H.; Wainberg, Zev A.; Kindler, Hedy; Wang-Gillam, Andrea; Oberstein, Paul; Morse, Michael A.; Zeh, Herbert J.; Weekes, Colin; Reid, Tony; Borazanci, Erkut; Crocenzi, Todd; LoConte, Noelle K.; Musher, Benjamin; Laheru, Daniel; Murphy, Aimee; Whiting, Chan; Nair, Nitya; Enstrom, Amanda; Ferber, Sandy; Brockstedt, Dirk G.; Jaffee, Elizabeth.

In: Clinical Cancer Research, Vol. 25, No. 18, 15.09.2019, p. 5493-5502.

Research output: Contribution to journalArticle

Le, D, Picozzi, VJ, Ko, AH, Wainberg, ZA, Kindler, H, Wang-Gillam, A, Oberstein, P, Morse, MA, Zeh, HJ, Weekes, C, Reid, T, Borazanci, E, Crocenzi, T, LoConte, NK, Musher, B, Laheru, D, Murphy, A, Whiting, C, Nair, N, Enstrom, A, Ferber, S, Brockstedt, DG & Jaffee, E 2019, 'Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study)', Clinical Cancer Research, vol. 25, no. 18, pp. 5493-5502. https://doi.org/10.1158/1078-0432.CCR-18-2992
Le, Dung ; Picozzi, Vincent J. ; Ko, Andrew H. ; Wainberg, Zev A. ; Kindler, Hedy ; Wang-Gillam, Andrea ; Oberstein, Paul ; Morse, Michael A. ; Zeh, Herbert J. ; Weekes, Colin ; Reid, Tony ; Borazanci, Erkut ; Crocenzi, Todd ; LoConte, Noelle K. ; Musher, Benjamin ; Laheru, Daniel ; Murphy, Aimee ; Whiting, Chan ; Nair, Nitya ; Enstrom, Amanda ; Ferber, Sandy ; Brockstedt, Dirk G. ; Jaffee, Elizabeth. / Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study). In: Clinical Cancer Research. 2019 ; Vol. 25, No. 18. pp. 5493-5502.
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abstract = "Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95{\%} confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95{\%} CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.",
author = "Dung Le and Picozzi, {Vincent J.} and Ko, {Andrew H.} and Wainberg, {Zev A.} and Hedy Kindler and Andrea Wang-Gillam and Paul Oberstein and Morse, {Michael A.} and Zeh, {Herbert J.} and Colin Weekes and Tony Reid and Erkut Borazanci and Todd Crocenzi and LoConte, {Noelle K.} and Benjamin Musher and Daniel Laheru and Aimee Murphy and Chan Whiting and Nitya Nair and Amanda Enstrom and Sandy Ferber and Brockstedt, {Dirk G.} and Elizabeth Jaffee",
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T1 - Results from a phase IIb, randomized, multicenter study of GVAX pancreas and CRS-207 compared with chemotherapy in adults with previously treated metastatic pancreatic adenocarcinoma (ECLIPSE study)

AU - Le, Dung

AU - Picozzi, Vincent J.

AU - Ko, Andrew H.

AU - Wainberg, Zev A.

AU - Kindler, Hedy

AU - Wang-Gillam, Andrea

AU - Oberstein, Paul

AU - Morse, Michael A.

AU - Zeh, Herbert J.

AU - Weekes, Colin

AU - Reid, Tony

AU - Borazanci, Erkut

AU - Crocenzi, Todd

AU - LoConte, Noelle K.

AU - Musher, Benjamin

AU - Laheru, Daniel

AU - Murphy, Aimee

AU - Whiting, Chan

AU - Nair, Nitya

AU - Enstrom, Amanda

AU - Ferber, Sandy

AU - Brockstedt, Dirk G.

AU - Jaffee, Elizabeth

PY - 2019/9/15

Y1 - 2019/9/15

N2 - Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.

AB - Purpose: Limited options exist for patients with advanced pancreatic cancer progressing after 1 or more lines of therapy. A phase II study in patients with previously treated metastatic pancreatic cancer showed that combining GVAX pancreas (granulocyte-macrophage colony-stimulating factor-secreting allogeneic pancreatic tumor cells) with cyclophosphamide (Cy) and CRS-207 (live, attenuated Listeria monocytogenes expressing mesothelin) resulted in median overall survival (OS) of 6.1 months, which compares favorably with historical OS achieved with chemotherapy. In the current study, we compared Cy/GVAX+CRS-207, CRS-207 alone, and standard chemotherapy in a three-arm, randomized, controlled phase IIb trial. Patients and Methods: Patients with previously treated metastatic pancreatic adenocarcinoma were randomized 1:1:1 to receive Cy/GVAX + CRS-207 (arm A), CRS-207 (arm B), or physician's choice of single-agent chemotherapy (arm C). The primary cohort included patients who had failed 2 prior lines of therapy, including gemcitabine. The primary objective compared OS between arms A and C in the primary cohort. The second-line cohort included patients who had received 1 prior line of therapy. Additional objectives included OS between all treatment arms, safety, and tumor responses. Results: The study did not meet its primary efficacy endpoint. At the final study analysis, median OS [95% confidence interval (CI)] in the primary cohort (N = 213) was 3.7 (2.9- 5.3), 5.4 (4.2-6.4), and 4.6 (4.2-5.7) months in arms A, B, and C, respectively, showing no significant difference between arm A and arm C [P = not significant (NS), HR = 1.17; 95% CI, 0.84-1.64]. The most frequently reported adverse events in all treatment groups were chills, pyrexia, fatigue, and nausea. No treatment-related deaths occurred. Conclusions: The combination of Cy/GVAX+CRS-207 did not improve survival over chemotherapy.

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