Cytokinetics, Incorporated (NASDAQ: CYTK) announced that a
poster presentation summarizing interim data from the Phase I portion
of a Phase I/II clinical trial evaluating ispinesib, a novel
inhibitor of kinesin spindle protein (KSP), in patients with locally
advanced or metastatic breast cancer was presented at the 2009 Annual
Meeting of the American Society of Clinical Oncology (ASCO) held from
May 29 - June 2, 2009 in Orlando, FL.  This poster highlights the
safety and tolerability of ispinesib and tumor-reductions of 30
percent in 3 patients in this ongoing Phase I/II clinical trial of
ispinesib dosed on days 1 and 15 of a 28-day cycle.  In this trial,
ispinesib appears to demonstrate anti-cancer activity with a similar
toxicity profile when compared with prior clinical trials conducted
with a once every 21 days dosing schedule.

“In the ongoing Phase I portion of this Phase I/II clinical trial, we
have observed signs of clinical activity for ispinesib in patients
with locally advanced or metastatic breast cancer without our having
yet reached the maximum-tolerated dose,” stated Henry Gomez, M.D.,
Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru.
“Amplification of the anti-cancer signal on this newer dosing
schedule, combined with a favorable tolerability profile, suggests
the potential for this drug candidate in the treatment of metastatic
breast cancer patients.”

“The dosing schedule, an intravenous 1-hour infusion on days 1 and 15
of a 28-day cycle, studied in this Phase I/II clinical trial appears
to be both well-tolerated and generating encouraging signs of
clinical activity,” stated Andrew A. Wolff, MD, FACC, Cytokinetics’
Senior Vice President of Clinical Research and Development and Chief
Medical Officer.  “We look forward to continuing the dose-escalation
of ispinesib in this trial as we explore the possible role of this
novel drug candidate in patients with metastatic breast cancer.”

Poster Presentation at ASCO

A poster titled, “A Phase I/II Trial of Ispinesib, a Kinesin Spindle
Protein (KSP) Inhibitor, Dosed q14d in Patients with Advanced Breast
Cancer Previously Untreated with Chemotherapy for Metastatic Disease
or Recurrence” was presented on Monday, June 1, 2009.  This poster
summarized interim data from the Phase I portion of an ongoing Phase
I/II clinical trial evaluating ispinesib in patients with advanced
breast cancer.  The primary objectives of the Phase I portion of this
clinical trial are to determine the dose-limiting toxicities (DLTs)
and maximum-tolerated dose and to assess the safety and tolerability
of ispinesib administered as a 1-hour intravenous infusion on days 1
and 15 of a 28-day cycle.  The secondary objectives are to
characterize the pharmacokinetics of ispinesib on this schedule and
to evaluate the potential effect of ispinesib on biomarkers of cell
proliferation in patients with accessible tumors.  The authors
concluded that one Response Evaluation Criteria in Solid Tumors
(RECIST)-confirmed partial response (PR) with a duration of 6 months
has been reported.  Also, two additional patients had a best response
of PR (unconfirmed), and 10 additional patients have had stable
disease not reaching PR criteria, four of which had a duration of 4
or more months. The authors also noted that protocol-defined DLTs of
Grade 3 ALT/AST increases with questionable relationship to study
drug were observed in two out of seven patients treated at the 14
mg/m2 dose level.  The 12 mg/m2 cohort has been expanded to six
patients with no observed DLTs.  The protocol has been amended to
further evaluate the 14 mg/m2 dose level.

Development Status of Ispinesib

Previously, in December 2008, at the San Antonio Breast Cancer
Symposium, Cytokinetics presented interim results from the Phase I
portion of its Phase I/II clinical trial of ispinesib. Interim data
demonstrated that this drug candidate was well-tolerated when
administered as a 1-hour intravenous infusion on days 1 and 15 of a
28-day cycle, with the most frequent adverse event being neutropenia.
The best responses observed to date were investigator-reported tumor
reductions of 30% or greater in the sum of the target lesion
diameter, reported in 3 patients. One of these patients had an
investigator-reported PR according to the RECIST.  Cytokinetics
continues to enroll and dose-escalate patients in the Phase I portion
of this trial.

In June 2007, Cytokinetics reported final results of a Phase II
clinical trial conducted by GlaxoSmithKline (GSK) designed to evaluate
the safety and efficacy of ispinesib in patients with locally
advanced or metastatic breast cancer whose disease had recurred or
progressed despite treatment with anthracyclines and taxanes.  In
that trial, patients received ispinesib as monotherapy at 18 mg/m2 as
a 1-hour intravenous infusion every 21 days.  The primary endpoint of
the trial was objective response by RECIST.  Partial responses,
observed in 4 of 45 evaluable patients, were confirmed by independent
radiology review and were seen in liver, lung and lymph node
metastases. The duration of these responses, also independently
reviewed, ranged from 6.9 weeks to 19.1 weeks.  The median time to
progression in the treated population was 5.9 weeks.  The adverse
events were manageable, predictable and consistent with those seen in
the Phase I trials of ispinesib.  The most common grade 3/4 adverse
events observed in the 50 patients evaluable for safety were
neutropenia (21 patients), febrile neutropenia (4 patients) and
neutropenic sepsis (1 patient).

Source
Cytokinetics