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

Abstract Lessons Learned The safety profile in the gemcitabine/simtuzumab group was similar to that in the gemcitabine/placebo group. The addition of simtuzumab to gemcitabine does not improve clinical outcomes in patients with metastatic 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 with metastatic 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 follow-up 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; p = .73), 3.5 months (1.13 0.76–1.66, p = .61]), and 3.7 months, respectively. Median OS was 7.6 months (0.83 0.57–1.22; p = .28), 5.9 months (1.07 0.73–1.55; p = .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.