An endothelin B receptor agonist
Route of Administration
Mode of Action
SPI-1620 is a highly selective peptide agonist of endothelin-B receptors, on endothelial cells, the innermost layer of cells lining the blood vessels.
This technology takes advantage of the fact that the blood supply to tumors is different than the blood supply to healthy organs. Blood vessels in the growing part of tumors are relatively devoid of smooth muscle covering and are rich in endothelial cells.
Therefore, by stimulating the endothelial-B receptors present on the endothelial cells, SPI-1620 should selectively increase tumor blood flow, and increase delivery of anticancer agents to the tumor, while sparing healthy tissue.
The current study is a Phase 1, open label, ascending dose study assessing the safety, tolerability, pharmacokinetics and pharmacodynamics of the endothelin B receptor agonist, SPI-1620, in patients with recurrent progressive carcinoma.
Chemotherapy is one of the mainstays of therapy for solid carcinomas, including breast, lung, and prostate. Chemotherapy uses drugs called cytotoxic agents that are poisonous to cells and kill cancer cells, as well as rapidly dividing normal cells. Chemotherapy often fails because adequate and uniform distribution of the cytotoxic agents is not achieved in the tumor, and serious side effects can result from toxicity to normal cells. Consequently, any means to increase the delivery of a cytotoxic agent selectively to tumors, while minimizing its concentration in normal tissues may be very beneficial.
SPI-1620 is being developed as an adjunct to chemotherapy. In pre-clinical studies, when anti-cancer drugs, such as paclitaxel injection, are administered shortly after SPI-1620, the anti-cancer drug concentration in the tumor is increased several fold.
This results in increased antitumor efficacy at a given dose of a cytotoxic agent, and might allow physicians to maximize efficacy with reduced cytotoxic agent doses with resultant decreased toxicity to the normal organs.