EntreMed, Inc., a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, announced commencement of a multi-centre study with its drug candidate, MKC-1, in non-small cell lung cancer (NSCLC) patients.
The lead institution for this phase 1/2, open label, dose escalation study will be the Indiana University Cancer Center in Indianapolis, Indiana. Nasser H. Hanna, M.D., Assistant Professor, Department of Medicine, Division of Hematology/Oncology at IUCCI, will serve as Principal Investigator. MKC-1 is being evaluated currently in phase 1 and 2 clinical studies against breast cancer and in patients with leukaemia.
The objective of the phase 1 portion of this study will be to assess the safety and maximum tolerated dose of MKC-1 when administered orally in combination with pemetrexed (Alimta).
Alimta is a multi-targeted antifolate, which blocks the activity of folic acid and is approved for the treatment of metastatic NSCLC.
The phase 2 component of this study will assess the antitumor activity and progression free survival (PFS) in up to 60 patients with non-small cell lung cancer. Patients whose disease has progressed following initial therapy may be eligible to enrol. Patients will receive orally administered MKC-1 in combination with pemetrexed (Alimta). A secondary endpoint of the phase 2 study will be to evaluate other parameters of antitumour activity including response duration and overall survival.
MKC-1 is a novel, orally active cell cycle inhibitor with in vitro and in vivo efficacy against a wide range of human solid tumour cell lines, including multi-drug resistant cell lines. MKC-1 has demonstrated broad-acting antitumour effects, showing tumour growth inhibition or regression in multiple animal models, including paclitaxel-resistant models. MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis. These effects are consistent with a mechanism resulting from MKC-1 binding to multiple intracellular targets, including tubulin and the importin â proteins. The importin â family of proteins plays a critical role in nuclear transport and cell division.
Dr. Nasser Hanna commented, "We look forward to initiating this important study to determine the effects that MKC-1 in combination with Alimta has against lung cancer." Carolyn F. Sidor, M.D., M.B.A., EntreMed's Vice President and Chief Medical Officer, further commented, "We continue to expand our development program for MKC-1. The NSCLC clinical trial represents the third clinical study initiated this year and our first clinical trial combining MKC-1 with an approved therapeutic agent. Dr. Hanna, the study's principal investigator, and his colleagues at the Indiana University Cancer Center participated in the initial clinical study of MKC-1 as a single agent in NSCLC patients. By combining MKC-1 with Alimta, we hope to improve the clinical benefit over either agent given alone in patients who have failed prior chemotherapy."