Phase II trial of single agent Val-boroPro (Talabostat) inhibiting Fibroblast Activation Protein in patients with metastatic colorectal cancer

Cancer Biol Ther. 2007 Nov;6(11):1691-9. doi: 10.4161/cbt.6.11.4874. Epub 2007 Aug 14.


Purpose: Fibroblast Activation Protein (FAP) is a tumor fibroblast protease that has been shown to potentiate colorectal cancer growth. The clinical impact of FAP inhibition was tested using Val-boroPro (Talabostat), the first clinical inhibitor of FAP enzymatic activity, in a phase II study of patients with metastatic colorectal cancer.

Methods: Patients with metastatic colorectal cancer who had previously received systemic chemotherapies were treated with single agent Val-boroPro 200 microg p.o. BID continuously. Eligibility included measurable disease, performance status of 0 to 2, and adequate organ function. Laboratory correlates evaluated the pharmacodynamic effects of Val-boroPro on FAP enzymatic function in the peripheral blood.

Results: Twenty-eight patients (median age 62; 12 males, 16 females) were enrolled in this study. There were no objective responses. Six of 28 (21%) patients had stable disease for a median of 25 weeks (range 11-38 weeks). Laboratory analysis demonstrated significant, although incomplete inhibition of FAP enzymatic activity in the peripheral blood.

Conclusion: This phase II trial of Val-boroPro demonstrated minimal clinical activity in patients with previously treated metastatic colorectal cancer. However it provides the initial proof-of-concept that physiologic inhibition of FAP activity can be accomplished in patients with colorectal cancer, and lays the groundwork for future studies targeting the tumor stroma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / blood
  • Boronic Acids / adverse effects
  • Boronic Acids / blood
  • Boronic Acids / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Dipeptides / adverse effects
  • Dipeptides / blood
  • Dipeptides / therapeutic use*
  • Endopeptidases
  • Female
  • Gelatinases
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasm Metastasis
  • Serine Endopeptidases / blood
  • alpha-2-Antiplasmin / analysis


  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Boronic Acids
  • Dipeptides
  • Membrane Proteins
  • alpha-2-Antiplasmin
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases
  • talabostat