Kosan Presents Phase 1 Data Showing Antitumor Activity and Safety Profile of Epothilone KOS-1584 at AACR/NCI/EORTC Meeting
HAYWARD, Calif., Oct. 23 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN) presented updated data today from a Phase 1 clinical trial showing that KOS-1584/R1645, an epothilone under co-development with Roche, demonstrated antitumor activity and tolerability in patients with solid tumors. KOS-1584/R1645 showed signs of activity in patients with non-small cell lung, ovarian, breast, prostate, pancreatic, head and neck and colon cancer. The Phase 1 trial explored two different schedules of KOS-1584/R1645 using escalating doses. Data reported today were from a trial investigating weekly dosing schedules (weekly 2 weeks out of 3 weeks and weekly 3 weeks out of 4 weeks). Common toxicities were generally low-grade and manageable.
Data from the Phase 1 trial of KOS-1584/R1645 were presented in a poster titled, 'Optimization of the Phase 2 Dose of KOS-1584 (a Novel, Synthetic Epothilone) via Weekly Administration,' by Howard Burris, M.D., Sarah Cannon Research Institute, Nashville, TN, at the 2007 Annual Meeting of the American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer (AACR/NCI/EORTC).
'We believe that KOS-1584 has the potential to achieve best-in-class status in the emerging epothilone market as well as to compete in the established taxane market,' said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. 'We look forward to our planned commencement of a Phase 2 clinical program for KOS-1584 toward the end of 2007.'
Phase 1 Trial Results of KOS-1584
The Phase 1 trial was designed to define the maximum tolerated dose, dose-limiting toxicity and recommended Phase 2 dose and to assess early activity of KOS-1584/R1645 when administered to patients with advanced solid tumors (who have no standard therapy options) on two dosing schedules. The Phase 1 trial enrolled 60 patients investigating a wide range of doses from 0.8 mg/m2 to 25 mg/m2 on the 3 of 4 week schedule and 16 to 30 mg/m2 on the 2 of 3 week schedule; the 1-hour and 3-hour durations of infusion were included on both schedules. Indications of antitumor activity included:
-- 1 confirmed partial response (PR) in a patient with advanced non-small
cell lung cancer (3 prior chemotherapy regimens); this patient had 44%
tumor shrinkage by RECIST withdrew after 10 months (10 cycles) and
remains in PR over one year later;
-- 1 patient with breast cancer (3 prior regimens, active on study at
Cycle 5) experienced a 40% reduction in tumor marker CA-15.3, 42.5%
reduction in CA27,29 and 30% reduction in CEA;
-- 1 patient with advanced ovarian cancer (4 prior regimens) had 40% tumor
marker CA125 decrease and 20% shrinkage of nodal disease (on study for
6 cycles);
-- 1 patient with advanced prostate cancer had 94% reduction in PSA and
improved nodal disease after cycle 2 and was on study for 6 months (6
cycles);
-- 1 patient with pancreatic cancer had a 39% decrease in CA19-9
after 4 cycles; and
-- 6 patients had stable disease (3 or more months), including those with
head and neck, pancreatic, colon, breast and non-small cell lung
cancers.
Common drug related toxicities varied depending on dose and dose schedule, and were predominantly gastrointestinal symptoms, primarily diarrhea, that were generally manageable with supportive care. Grade 3 neuropathy was limited to one patient at the recommended dose on the 4-week schedule and two patients at the highest doses tested on the 3-week schedule. The recommended Phase 2 dose will be based on clinical activity, dose intensity, side effect profile and schedule compatibility with established chemotherapy regimens: 36 mg/m2 every 3 weeks; or 25 mg/m2 twice every 3 weeks depending on data from expanded dose cohorts.
surf's up......crikey
