A tumor necrosis factor receptor loop peptide mimic inhibits bone destruction to the same extent as anti–tumor necrosis factor monoclonal antibody in murine collagen-induced arthritis

2007 ◽  
Vol 56 (4) ◽  
pp. 1164-1174 ◽  
Author(s):  
Hiroaki Saito ◽  
Takefumi Kojima ◽  
Mariko Takahashi ◽  
William C. Horne ◽  
Roland Baron ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Bone Destruction ◽  
Collagen Induced Arthritis ◽  
Peptide Mimic ◽  
Necrosis Factor

A phase Ib study to assess the safety of lexatumumab, a human monoclonal antibody that activates TRAIL-R2, in combination with gemcitabine, pemetrexed, doxorubicin or FOLFIRI

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14006-14006 ◽  
Author(s):  
B. I. Sikic ◽  
H. A. Wakelee ◽  
M. von Mehren ◽  
N. Lewis ◽  
A. H. Calvert ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Tumor Necrosis Factor Receptor ◽  
Chemotherapeutic Agents ◽  
Extrinsic Pathway ◽  
Wide Range ◽  
Necrosis Factor

14006 Background: Lexatumumab (HGS-ETR2) is a fully-human agonistic monoclonal antibody that targets and activates the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor 2 (TRAIL-R2). TRAIL-R2 is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily that, when activated, induces apoptosis via the extrinsic pathway. Lexatumumab shows promising anti-tumor activity in preclinical models, particularly in combination with chemotherapeutic agents. Single-agent lexatumumab was well-tolerated in phase I trials. This is the first study of the safety of a TRAIL-R2 agonist in combination with chemotherapy. Methods: Patients for whom gemcitabine, pemetrexed, doxorubicin or FOLFIRI was considered an appropriate treatment received one of the full-dose chemotherapy regimens plus lexatumumab every 2 weeks (for gemcitabine and FOLFIRI) or 3 weeks (for pemetrexed and doxorubicin). Four to 6 patients were treated with 5 mg/kg lexatumumab in each chemotherapy cohort prior to dose escalation to 10 mg/kg. Results: To date, 41 patients with a wide range of cancer types have received 164 courses of lexatumumab over the 2 dose levels. The majority (33/41) received at least 2 courses (range 1 to 19). Lexatumumab was well-tolerated; no dose reductions of lexatumumab were required. Severe adverse events considered at least possibly related to lexatumumab included anemia, fatigue and dehydration. Tumor shrinkage has been observed, including confirmed partial responses (PRs) in the FOLFIRI and doxorubicin arms. Eight patients continue on study. Conclusions: Lexatumumab can be safely administered in combination with a wide range of chemotherapeutic agents. Evaluation of the efficacy of lexatumumab in combination with chemotherapy in Phase 2 trials is warranted. [Table: see text]

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