A phase II randomized, double-blind, placebo-controlled study of simtuzumab or placebo in combination with gemcitabine for the first-line treatment of pancreatic adenocarcinoma

Al B. Benson, Zev A. Wainberg, J. Randolph Hecht, Dmitry Vyushkov, Hua Dong, Johanna Bendell, Fred Kudrik

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background. The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. Methods. Adult patients withmetastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results. Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median followup of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], p value vs placebo: 1.09 [0.74-1.61]; p5.73), 3.5 months (1.13 [0.76-1.66], p5.61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22]; p5.28), 5.9 months (1.07 [0.73-1.55]; p5.69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated. Conclusion. The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.

Original languageEnglish (US)
JournalOncologist
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2017

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gemcitabine
Adenocarcinoma
Placebos
Therapeutics
Disease-Free Survival
Protein-Lysine 6-Oxidase
Antibodies, Monoclonal, Humanized
Survival
Extracellular Matrix

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Benson, Al B. ; Wainberg, Zev A. ; Randolph Hecht, J. ; Vyushkov, Dmitry ; Dong, Hua ; Bendell, Johanna ; Kudrik, Fred. / A phase II randomized, double-blind, placebo-controlled study of simtuzumab or placebo in combination with gemcitabine for the first-line treatment of pancreatic adenocarcinoma. In: Oncologist. 2017 ; Vol. 22, No. 3.
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abstract = "Background. The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. Methods. Adult patients withmetastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results. Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median followup of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95{\%} confidence interval [CI], p value vs placebo: 1.09 [0.74-1.61]; p5.73), 3.5 months (1.13 [0.76-1.66], p5.61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22]; p5.28), 5.9 months (1.07 [0.73-1.55]; p5.69), and 5.7 months, respectively. ORRs were 13.9{\%}, 14.5{\%}, and 23.5{\%}, respectively. Simtuzumab was well tolerated. Conclusion. The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.",
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A phase II randomized, double-blind, placebo-controlled study of simtuzumab or placebo in combination with gemcitabine for the first-line treatment of pancreatic adenocarcinoma. / Benson, Al B.; Wainberg, Zev A.; Randolph Hecht, J.; Vyushkov, Dmitry; Dong, Hua; Bendell, Johanna; Kudrik, Fred.

In: Oncologist, Vol. 22, No. 3, 01.03.2017.

Research output: Contribution to journalArticle

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AU - Benson, Al B.

AU - Wainberg, Zev A.

AU - Randolph Hecht, J.

AU - Vyushkov, Dmitry

AU - Dong, Hua

AU - Bendell, Johanna

AU - Kudrik, Fred

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N2 - Background. The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. Methods. Adult patients withmetastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results. Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median followup of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], p value vs placebo: 1.09 [0.74-1.61]; p5.73), 3.5 months (1.13 [0.76-1.66], p5.61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22]; p5.28), 5.9 months (1.07 [0.73-1.55]; p5.69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated. Conclusion. The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.

AB - Background. The humanized IgG4 monoclonal antibody simtuzumab inhibits the extracellular matrix-remodeling enzyme lysyl oxidase-like 2 maintaining pathological stroma in tumors. Methods. Adult patients withmetastatic pancreatic adenocarcinoma (mPaCa) were randomly assigned to receive intravenous gemcitabine, 1,000 mg/m2, in combination with 200 or 700 mg simtuzumab or placebo. Primary endpoint was progression-free survival (PFS), secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. Results. Of 240 patients, 80 were randomly assigned to gemcitabine/simtuzumab 700 mg, 79 to gemcitabine/simtuzumab 200 mg, and 81 to gemcitabine/placebo. After a median followup of 3.0, 1.9, and 3.4 months for gemcitabine/simtuzumab 700 mg, gemcitabine/simtuzumab 200 mg, and gemcitabine/placebo, respectively, the median PFS was 3.7 months (adjusted hazard ratio [HR], 95% confidence interval [CI], p value vs placebo: 1.09 [0.74-1.61]; p5.73), 3.5 months (1.13 [0.76-1.66], p5.61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 [0.57-1.22]; p5.28), 5.9 months (1.07 [0.73-1.55]; p5.69), and 5.7 months, respectively. ORRs were 13.9%, 14.5%, and 23.5%, respectively. Simtuzumab was well tolerated. Conclusion. The addition of simtuzumab to gemcitabine did not improve clinical outcomes in patients with mPaCa.

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