The Phase II single-agent study is being conducted at multiple centers across the US to evaluate the safety and efficacy of MKC-1 in metastatic breast cancer patients who have failed therapy with anthracyclines and taxanes.
EntreMed said that results from the first stage of the single-agent study demonstrate that orally administered MKC-1 is well-tolerated without evidence of cumulative toxicity in anthracycline/taxane refractory metastatic breast cancer patients.
Of the 35 evaluable patients, one complete response (CR), two partial responses (PR), and three stable diseases (SD) of greater than four months were observed. This study has proceeded to the second stage and is continuing to enroll up to 53 evaluable patients to confirm safety and assess the extent of objective responses in this patient population.
MKC-1 is a novel, orally active, small molecule cell cycle inhibitor with a unique mechanism of action, which involves inhibition of the Akt-mTOR pathway, binding importin-b and tubulin, cell cycle arrest and apoptosis.
MKC-1 arrests mitosis by inhibiting an intracellular target important in cellular trafficking that has been shown to be involved in cell division. MKC- 1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase of the cell cycle, and induce apoptosis in multiple cell lines, consistent with a mechanism in which MKC-1 blocks the nuclear uptake of proteins essential to cell replication.
Carolyn Sidor, EntreMed's vice president and chief medical officer, commented on the results: “MKC-1 is showing good antitumor activity in metastatic breast cancer patients who had failed conventional anthracycline and taxane chemotherapy. In addition, the study has passed a second data safety monitoring board (DSMB) review without any study modification.”
“An additional MKC-1 single-agent study is underway in hematological cancers and a combination study is underway with pemetrexed (Alimta) in non-small cell lung cancer. We plan to evaluate our options for either randomized single- agent or combination studies in breast cancer once this study is complete,” she added.