TY - JOUR
T1 - A phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer
AU - Scott, Andrew M.
AU - Wiseman, Greg
AU - Welt, Sydney
AU - Adjei, Alex
AU - Lee, Fook Thean
AU - Hopkins, Wendie
AU - Divgi, Chaitan R.
AU - Hanson, Lorelei H.
AU - Mitchell, Paul
AU - Gansen, Denise N.
AU - Larson, Steven M.
AU - Ingle, James N.
AU - Hoffman, Eric W.
AU - Tanswell, Paul
AU - Ritter, Gerd
AU - Cohen, Leonard S.
AU - Bette, Peter
AU - Arvay, Lisa
AU - Amelsberg, Andree
AU - Vlock, Dan
AU - Rettig, Wolfgang J.
AU - Old, Lloyd J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Purpose: The purpose of this research was to determine the safety, immunogenicity, pharmacokinetics, biodistribution, and tumor uptake of repeat infusions of a complementarity-determining region grafted humanized antibody (sibrotuzumab) directed against human fibroblast activation protein (FAP). Experimental Design: A Phase I open-label dose escalation study was conducted in patients with cancers epidemiologically known to be FAP positive. Patients were entered into one of four dosage tiers of 5, 10, 25, or 50 mg/m2 sibrotuzumab, administered weekly for 12 weeks, with trace labeling with 8-10 mCi of 131I in weeks 1, 5, and 9. Results: A total of 26 patients were entered into the trial (15 males and 11 females; mean age, 59.9 years; age range, 41-81 years). Twenty patients had colorectal carcinoma, and 6 patients had non-small cell lung cancer. A total of 218 infusions of sibrotuzumab were administered during the first 12 weeks of the study, with 24 patients being evaluable. One patient received an additional 96 infusions on continued-use phase for a total of 108 infusions over a 2-year period, and 1 patient received an additional 6 infusions on continued use. There were no objective tumor responses. Only one episode of dose-limiting toxicity was observed. Therefore, a maximum tolerated dose was not reached. Treatment-related adverse events were observed in 6 patients during the infusional monitoring period. Four of the 6 patients, 3 of whom had associated positive serum human antihuman antibody, were removed from the study because of clinical immune responses. Gamma camera images of [131I]sibrotuzumab demonstrated no normal organ uptake of sibrotuzumab, with tumor uptake evident within 24-48 h after infusion. Analysis of pharmacokinetics demonstrated a similar mean terminal t1/2 of 1.4-2.6 days at the 5, 10, and 25 mg/m2 dose levels, and with a longer mean t1/2 of 4.9 days at the 50 mg/m2 dose level. Conclusion: Repeat infusions of the humanized antiFAP antibody sibrotuzumab can be administered safely to patients with advanced FAP-positive cancer.
AB - Purpose: The purpose of this research was to determine the safety, immunogenicity, pharmacokinetics, biodistribution, and tumor uptake of repeat infusions of a complementarity-determining region grafted humanized antibody (sibrotuzumab) directed against human fibroblast activation protein (FAP). Experimental Design: A Phase I open-label dose escalation study was conducted in patients with cancers epidemiologically known to be FAP positive. Patients were entered into one of four dosage tiers of 5, 10, 25, or 50 mg/m2 sibrotuzumab, administered weekly for 12 weeks, with trace labeling with 8-10 mCi of 131I in weeks 1, 5, and 9. Results: A total of 26 patients were entered into the trial (15 males and 11 females; mean age, 59.9 years; age range, 41-81 years). Twenty patients had colorectal carcinoma, and 6 patients had non-small cell lung cancer. A total of 218 infusions of sibrotuzumab were administered during the first 12 weeks of the study, with 24 patients being evaluable. One patient received an additional 96 infusions on continued-use phase for a total of 108 infusions over a 2-year period, and 1 patient received an additional 6 infusions on continued use. There were no objective tumor responses. Only one episode of dose-limiting toxicity was observed. Therefore, a maximum tolerated dose was not reached. Treatment-related adverse events were observed in 6 patients during the infusional monitoring period. Four of the 6 patients, 3 of whom had associated positive serum human antihuman antibody, were removed from the study because of clinical immune responses. Gamma camera images of [131I]sibrotuzumab demonstrated no normal organ uptake of sibrotuzumab, with tumor uptake evident within 24-48 h after infusion. Analysis of pharmacokinetics demonstrated a similar mean terminal t1/2 of 1.4-2.6 days at the 5, 10, and 25 mg/m2 dose levels, and with a longer mean t1/2 of 4.9 days at the 50 mg/m2 dose level. Conclusion: Repeat infusions of the humanized antiFAP antibody sibrotuzumab can be administered safely to patients with advanced FAP-positive cancer.
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M3 - Article
C2 - 12738716
AN - SCOPUS:0037989982
SN - 1078-0432
VL - 9
SP - 1639
EP - 1647
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 5
ER -