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Sub-category:
Tyrosine Kinase Inhibitors
Category:
Developmental Therapeutics: Molecular Therapeutics
Meeting:
2008 ASCO Annual Meeting
Session Type and Session Title:
This abstract will not be presented at the 2008 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract No:
14657
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 14657)
Author(s):
L. H. Camacho, S. L. Moulder, P. M. LoRusso, G. R. Blumenschein, P. J. Bristow, R. Kurzrock, S. Fu, K. Schlienger, D. A. Bergstrom
Abstract:
Background: MK-2461 is a potent small molecule inhibitor of c-Met, a receptor tyrosine kinase involved in tumor cell proliferation and motility. Over-expression of c-Met or Met gene amplification has been associated with poorer prognosis in several tumor types. Methods: Multicenter, open-label, phase I dose escalation study in patients with advanced solid tumors refractory to standard therapy. Drug was administered by mouth daily or twice daily (BID) for 28 days followed by a 14 day rest period during cycle 1. Patients received continuous dosing subsequently for 28-day cycles. Maximum tolerated dose (MTD) was determined using a standard 3+3 dosing design. PK analyses were performed on days 1 and 28 of cycle 1. Results: Fourteen patients (10 M/ 4 F), mean age 54 (range 19-76), have received 31 cycles (range 1-6). Dose levels tested include 60mg daily, 60mg BID, 120mg BID, and 180 mg BID. Toxicity data are available for 11 patients treated at the 60mg daily-120mg BID dosing cohorts. Ten patients (91%) have not experienced > Grade 1 drug-related toxicity. Dose limiting toxicity has not been reached and no objective antitumor responses have been observed. One patient with mucinous carcinoma of the appendix had stable disease for 6 cycles. Common drug related toxicities are outlined in the table below. Four patients experienced serious adverse experiences that were considered not related to MK-2461. PK analysis revealed a rapid Tmax (1-3 hr) across all dosing cohorts with a terminal half life of 6.3 hr following the final day of dosing for the QD dosing cohort. Conclusions: Twice daily administration of MK-2461 at the doses tested is well tolerated. Terminal t1/2 suggests acceptable drug plasma concentrations expected at BID dosing. Dose escalation continues. | Toxicity | Grade 1 (%) | Grade 2 (%) | | Anorexia | 2(18%) | 0 | | Fatigue | 1(9%) | 1(9%) | | Nausea | 1(9%) | 0 |
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by L. H. Camacho :
Presentations by L. H. Camacho :
Educational Book Manuscripts by L. H. Camacho :
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