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

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/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 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.