A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer

To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally adv...

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Veröffentlicht in:Annals of surgery Jg. 275; H. 1; S. 45
Hauptverfasser: Hewitt, Daniel Brock, Nissen, Nicholas, Hatoum, Hassan, Musher, Benjamin, Seng, John, Coveler, Andrew L, Al-Rajabi, Raed, Yeo, Charles J, Leiby, Benjamin, Banks, Joshua, Balducci, Lodovico, Vaccaro, Gina, LoConte, Noelle, George, Thomas J, Brenner, Warren, Elquza, Emad, Vahanian, Nicholas, Rossi, Gabriela, Kennedy, Eugene, Link, Charles, Lavu, Harish
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Veröffentlicht: United States 01.01.2022
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Abstract To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. ClinicalTrials.gov Identifier: NCT01836432.
AbstractList To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. ClinicalTrials.gov Identifier: NCT01836432.
To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC).OBJECTIVESTo compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC).To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene.SUMMARY BACKGROUND DATATo date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene.A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival.METHODSA multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival.Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).RESULTSBetween May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (interquartile range) overall survival was 14.9 (12.2-17.8) months in the standard group (N = 158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) [hazard ratio (HR) 1.02, 95% confidence intervals 0.66-1.58; P = 0.98]. Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% confidence intervals 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation.CONCLUSIONSAlgenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation.ClinicalTrials.gov Identifier: NCT01836432.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01836432.
Author Hatoum, Hassan
Elquza, Emad
Rossi, Gabriela
Seng, John
Al-Rajabi, Raed
Coveler, Andrew L
Lavu, Harish
LoConte, Noelle
George, Thomas J
Yeo, Charles J
Leiby, Benjamin
Banks, Joshua
Vaccaro, Gina
Kennedy, Eugene
Musher, Benjamin
Hewitt, Daniel Brock
Vahanian, Nicholas
Brenner, Warren
Nissen, Nicholas
Link, Charles
Balducci, Lodovico
Author_xml – sequence: 1
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  organization: University of Oklahoma, Oklahoma City, Oklahoma
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  organization: Baylor College of Medicine, Houston, Texas
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  organization: Virginia Piper Cancer Institute, Minneapolis, Minnesota
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  organization: University of Kansas Cancer Center, Westwood, Kansas
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  surname: Yeo
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  organization: Thomas Jefferson University Hospital and The Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, Pennsylvania
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  surname: Leiby
  fullname: Leiby, Benjamin
  organization: Thomas Jefferson University Hospital and The Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, Pennsylvania
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  fullname: Banks, Joshua
  organization: Thomas Jefferson University Hospital and The Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, Pennsylvania
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  surname: Balducci
  fullname: Balducci, Lodovico
  organization: H. Lee Moffitt Cancer Center, Tampa, Florida
– sequence: 12
  givenname: Gina
  surname: Vaccaro
  fullname: Vaccaro, Gina
  organization: Oregon Health and Science University, Portland, Oregon
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  givenname: Noelle
  surname: LoConte
  fullname: LoConte, Noelle
  organization: University of Wisconsin, Madison, Wisconsin
– sequence: 14
  givenname: Thomas J
  surname: George
  fullname: George, Thomas J
  organization: University of Florida, Gainesville, Florida
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  fullname: Brenner, Warren
  organization: Boca Raton Hospital, Boca Raton, Florida
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  givenname: Emad
  surname: Elquza
  fullname: Elquza, Emad
  organization: University of California at Irvine, Irvine, California
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  organization: NewLink Genetics Corporation, Ames, Iowa
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  organization: NewLink Genetics Corporation, Ames, Iowa
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  organization: Lumos Pharma Inc, Ames, Iowa
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  organization: NewLink Genetics Corporation, Ames, Iowa
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  surname: Lavu
  fullname: Lavu, Harish
  organization: Thomas Jefferson University Hospital and The Jefferson Pancreas, Biliary and Related Cancer Center, Philadelphia, Pennsylvania
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PublicationTitle Annals of surgery
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References 35284521 - Hepatobiliary Surg Nutr. 2022 Feb;11(1):115-118
34430537 - Hepatobiliary Surg Nutr. 2021 Aug;10(4):534-537
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Snippet To compare the efficacy and safety of algenpantucel-L [HyperAcute-Pancreas algenpantucel-L (HAPa); IND# 12311] immunotherapy combined with standard of care...
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StartPage 45
SubjectTerms Aged
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cancer Vaccines - adverse effects
Cancer Vaccines - therapeutic use
Deoxycytidine - adverse effects
Deoxycytidine - analogs & derivatives
Deoxycytidine - therapeutic use
Female
Fluorouracil - adverse effects
Fluorouracil - therapeutic use
Humans
Immunotherapy - adverse effects
Irinotecan - adverse effects
Irinotecan - therapeutic use
Leucovorin - adverse effects
Leucovorin - therapeutic use
Male
Middle Aged
Neoadjuvant Therapy - adverse effects
Oxaliplatin - adverse effects
Oxaliplatin - therapeutic use
Paclitaxel - adverse effects
Paclitaxel - therapeutic use
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - surgery
Pancreatic Neoplasms - therapy
Progression-Free Survival
Standard of Care
Survival Analysis
Title A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer
URI https://www.ncbi.nlm.nih.gov/pubmed/33630475
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