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

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/ m(2), 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 [0.731.55]; 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.