Ispinesib is a novel small molecule drug candidate that inhibits cell proliferation and promotes cancer cell death by specifically disrupting the function of a cytoskeletal protein known as kinesin spindle protein, or KSP. Current drugs that inhibit cell proliferation, such as paclitaxel and docetaxel, are standard treatments for many types of cancers, but these drugs also target other proteins that are essential to other important cellular functions and thus, their use is limited by side effects.
Ispinesib has been tested in a wide range of tumor types, and we believe the most promising results have been observed in breast cancer. Based on data presented to date, Cytokinetics has initiated a focused, open-label, non-randomized Phase I/II clinical trial designed to evaluate ispinesib monotherapy as a first-line treatment in chemotherapy-naïve patients with locally advanced (Stage IIIB) or metastatic (Stage IV) breast cancer. For more information regarding ispinesib and current and completed clinical trials, please visit the links below:
Development Status
Ongoing Clinical Trials Details
We are conducting a focused development program for ispinesib in breast cancer specifically designed to supplement the Phase I and Phase II clinical trials that demonstrated clinical activity in the treatment of patients with metastatic breast cancer and an acceptable tolerability profile for ispinesib in combination with capecitabine. Under this development program we recently initiated a Phase I/II clinical trial, the objective of which is to evaluate the possibility that ispinesib administered as monotherapy on days 1 and 15 of a 28-day cycle may demonstrate a more amplified signal of clinical activity in chemotherapy-naïve breast cancer patients than had been seen in earlier Phase II studies of ispinesib, conducted on an alternative dosing schedule and in more chemorefractory patients.
Phase II Clinical Trials Details
Prior to the current Phase I/II trial being initiated, Ispinesib had been the subject of a broad Phase II clinical trials program, including three Phase II clinical trials, one evaluating ispinesib as second- or third-line treatment for patients with locally advanced or metastatic breast cancer, one evaluating ispinesib as second-line treatment for patients with non-small cell lung cancer, and one evaluating ispinesib as second-line treatment for patients with advanced ovarian cancer. To date, clinical activity with ispinesib has been observed in breast cancer as well as in ovarian and non-small cell lung cancer, with the most robust clinical activity observed in a Phase II clinical trial evaluating ispinesib in the treatment of patients with locally advanced or metastatic breast cancer that failed to respond or recurred after treatment with taxanes and anthracyclines.
The NCI sponsored additional Phase II clinical trials, one evaluating the potential efficacy of ispinesib in the second-line treatment of patients with colorectal cancer, one in the first-line treatment of patients with hepatocellular cancer, one in the first-line treatment of patients with melanoma, one in the first- or second-line treatment of patients with head and neck cancers, one in the second-line treatment of patients with hormone-refractory prostate cancer, and one in the second-line treatment of patients with renal cell cancer. Data have been reported for all of these trials.
Phase Ib Clinical Trials Details
In addition, we conducted three dose-escalating Phase Ib clinical trials of ispinesib. Each of these trials was designed to evaluate the safety, tolerability and pharmacokinetics of ispinesib in combination with a leading anti-cancer therapeutic, one in combination with carboplatin, the second in combination with capecitabine, and the third in combination with docetaxel. The Phase Ib clinical trials of ispinesib in combination with carboplatin and docetaxel were completed in 2006 and demonstrated that ispinesib has an acceptable tolerability profile in combination with these standard chemotherapeutic agents. The clinical trial evaluating ispinesib in combination with capecitabine was completed in 2008 and also indicated that ispinesib has an acceptable tolerability profile in combination with capecitabine.
Phase I Clinical Trials Details
The NCI completed patient treatment in a Phase I clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of ispinesib on an alternative dosing schedule in patients with advanced solid tumors that failed to respond to all standard therapies. Data from this trial have been reported.
The NCI is continuing patient enrollment in a Phase I clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of ispinesib on an alternative dosing schedule in patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia in blast crisis or advanced myelodysplastic syndromes.
