In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 8093-8093
Abstract:
8093 Background: Activation of the hepatocyte growth factor (HGF)/MET receptor pathway promotes tumor growth, invasion and dissemination. LY is a humanized IgG4 monoclonal bivalent antibody against MET which inhibits ligand dependent- and ligand independent activation of MET. Based on preclinical results, we examined LY alone in patients with advanced solid tumors and LY+E in advanced NSCLC patients. Methods: LY monotherapy was administered 20-2,000 mg Q2W IV to 23 patients with advanced solid tumors. Combination therapy with 700-2,000 mg Q2W IV of LY and E (150 mg QD) was completed in 14 patients with advanced NSCLC. The primary objective was to determine a recommended phase II dose (RPTD) for LY and LY+E. Secondary objectives included assessment of toxicity, PK, PD (including MET extracelluar domain and HGF), and antitumor activity. Results: LY and LY+E were well tolerated. No dose-limiting toxicities, serious adverse events, or ≥ Grade 3 adverse events (AEs) possibly related to LY have been observed. The most frequent (≥5% of patients) AEs possibly related to LY2875358 monotherapy were nausea (8.7 %), vomiting (8.7%), and diarrhea (8.7%). The most frequent (≥10% of patient) grade 1 or 2 adverse event possibly related to LY2875358 in patients treated with LY+E were fatigue (21.4%) and anorexia (14.3%). Durable PR according to RECIST were observed for LY (n=1) and LY+E (n=2 out of 13 evaluable patients; both PR patients positive for MET protein expression). Conclusions: LY appears to be safe when administered as single agent and in combination with E up to 2,000 mg Q2W IV. The RPTD of LY is 750 mg Q2W IV for monotherapy and in combination with E based on PK/PD data. Clinical trial information: NTC 01287546.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.8093
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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