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 under a collaboration with GlaxoSmithKline, 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
Under a November 2006 amendment to our collaboration and license agreement with GSK, we assumed responsibility for the costs and activities associated with the continued development of the kinesin spindle protein (KSP) inhibitors ispinesib and SB-743921, subject to GSK’s option to resume responsibility for some or all development and commercialization activities associated with each of these novel drug candidates.
We are conducting a focused development program for ispinesib in breast cancer specifically designed to supplement the Phase I and Phase II clinical trials sponsored by GSK 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.
In addition, the National Cancer Institute (NCI) is continuing pateint enrollment in a Phase I clinical trial designed to evaluate the safety, tolerability and pharmacokinetics of ispinesib on an alternate dosing schedule in pediatric patients with relapsed or refractory solid tumors.
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 under the sponsorship of GSK and is still being developed in collaboration with the National Cancer Institute (NCI). GSK sponsored 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, GSK sponsored 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 is closed to enrollment. Final data from this trial are expected in 2008.
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.
