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

Abstract

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.

• Authors: Kalyani Narra, Stefanie R Mullins, Hyung-Ok Lee, Brenda Strzemkowski-Brun, Kimberly Magalong, Victoria J Christiansen, Patrick A McKee, Brian Egleston, Steven J Cohen, Louis M Weiner, Neal J Meropol, Jonathan D Cheng
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 6 Issue 11 Pg. 1691-9 (Nov 2007) ISSN: 1555-8576 [Electronic] United States
• PMID: 18032930 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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