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


CONCLUSIONS
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.
Narra
Kalyani
K
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Mullins
Stefanie R
SR
Lee
Hyung-Ok
HO
Strzemkowski-Brun
Brenda
B
Magalong
Kimberly
K
Christiansen
Victoria J
VJ
McKee
Patrick A
PA
Egleston
Brian
B
Cohen
Steven J
SJ
Weiner
Louis M
LM
Meropol
Neal J
NJ
Cheng
Jonathan D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000097:blood; D001897:Boronic Acids / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004151:Dipeptides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012697:Serine Endopeptidases / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis; D000099167:Fibroblast Activation Protein Alpha
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D004151:Dipeptides; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000979:alpha-2-Antiplasmin; D000099167:Fibroblast Activation Protein Alpha; C514044:talabostat