An open-label, dose escalation, safety, and pharmacokinetic study of
ENMD-2076 administered orally to patients with advanced cancer.
Sub-category: Other Novel Agents
Category: Developmental Therapeutics: Molecular Therapeutics
Meeting: 2009 ASCO Annual MeetingCitation: J Clin Oncol 27:15s, 2009 (suppl; abstr 3520)
Abstract No: 3520Author(s):
Background: ENMD-2076, a novel, orally-active antimitotic and antiangiogenic molecule inhibits Aurora A as well as tyrosine kinases that drive tumor vascularization, including VEGFR2 (KDR), PDGFR and the FGF receptors. This Phase 1 study was designed to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of ENMD-2076 administered once daily to patients (pts) with advanced cancer. Methods: The dose escalation scheme utilizes 3 (or 4) + 3 (or 2) design. Pts receive ENMD-2076 once daily in 28-day cycles (followed by 7-14 days of rest between cycles 1 and cycle 2 only). Results: 14 pts have been enrolled in 3 dose cohorts (range 60 to 120 mg/m2/d). Median age/performance status is 62/1. The total number of treatment cycles to date is 45, with a median of 3 cycles (range <1 n="14)">2/d. Following drug interruption, the pt restarted at 30 mg/m2/d and continued for 4 additional cycles before being removed for progressive disease. Noncompartmental PK analysis of the first two dose levels shows that the plasma concentration of ENMD-981693 (the active free base of ENMD-2076) is dose- linear, as reflected in AUC and Cmax. The estimated terminal half-life (t1/2) is unaltered regardless of dose; however, t1/2 is approximately 50% greater at steady state than following single dose administration. Four ovarian cancer and 2 colon cancer pts have achieved decreases ranging from 11-61% in either CA125 or CEA, respectively (4 are associated with stable disease at Cycle 2 by modified RECIST criteria). Serum KDR concentrations assayed by ELISA decreased from baseline in all patients on treatment from a mean of 9153 pg/mL (SEM 464.2) at D1 to 6987 pg/mL (SEM 460.0) at D28 (p <0.05).>Conclusions: ENMD-2076 is a small molecule kinase inhibitor with acceptable toxicity and preliminary evidence of antitumor activity in pts with ovarian and colorectal cancers.
(The final bold is mine.)
If this is true, this could be HUGE!!!!!!!!! This is on actual patients, people!!
I love you, Entremed researchers and docs involved with this clinical trial. With all my heart.Tune in to the annual ASCO meeting on May 30, 2009 for the actual presentation of trial results. Or my blog.
John Crewdson, are you still out there?
NOTE: So I am not accused of going all New York Times, May 3, 1998 on you (here), I would like to point out that this is just a Phase I trial.