A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the Second-Line treatment of metastatic KRAS mutant colorectal adenocarcinoma

J. Randolph Hecht*, Al B. Benson, Dmitry Vyushkov, Yingsi Yang, Johanna Bendell, Udit Verma

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations


Background. Simtuzumab, a humanized IgG4 monoclonal antibody to lysyl oxidase-like 2 (LOXL2), blocks desmoplastic reaction in colorectal carcinoma (CRC) cells in vitro. Methods. Patients with metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutant CRC were randomized to receive second-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) with either 200 or 700 mg simtuzumab or placebo every 2 weeks in cycles of 28 days. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety were assessed. Results. In total, 249 patients were randomized and treated with FOLFIRI/simtuzumab 700 mg (n584), FOLFIRI/simtuzumab 200 mg (n585), and FOLFIRI/placebo (n580). After a median follow-up of 5.1, 3.8, and 5.5 months, respectively, median PFS for each of the respective treatment groups was 5.5 months (adjusted HR [95% CI], p value versus placebo; 1.32 [0.92, 1.89]; p5.10), 5.4 months (1.45 [1.01, 2.06]; p5.04), and 5.8 months.Median OS was 11.4 months (1.23 [0.80, 1.91]; p5.25), 10.5 months (1.50 [0.98, 2.30]; p5.06), and 16.3 months, respectively. ORR was 11.9%, 5.9%, and 10%, respectively. Simtuzumab was tolerable in metastatic KRAS mutant CRC patients. Conclusion. The addition of simtuzumab to FOLFIRI did not improve clinical outcomes in patients with metastatic KRAS mutant CRC.

Original languageEnglish (US)
Pages (from-to)243-244 and e16-e23
Issue number3
StatePublished - Mar 2017


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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