Kosan Presents Preliminary Phase 2 Data Showing Antitumor Activity of Hsp90 Inhibitor Tanespimycin in Metastatic Melanoma at ASCO
Monday June 4, 6:00 am ET
HAYWARD, Calif., June 4 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) presented preliminary data from a Phase 2 monotherapy trial showing that tanespimycin demonstrated antitumor activity and tolerability in patients with metastatic melanoma, including one patient with a BRAF mutation (V600E) who had failed prior chemotherapy (within 6 weeks of initiation) and while on tanespimycin demonstrated progression-free survival for more than six months and 20% lesion reduction by RECIST as well as reduction in the size and number of extensive subcutaneous nodules. Data from the ongoing trial were presented on Sunday, June 3, 2007, by Richard Kefford, M.D., Ph.D., Westmead Hospital, University of Sydney, Australia, in a poster titled, "Phase 2 Trial of Tanespimycin (KOS-953), a Heat Shock Protein-90 (Hsp90) Inhibitor in Patients with Metastatic Melanoma," at the 2007 Annual Meeting of the American Society of Clinical Oncology (ASCO).
"Hsp90 inhibition is of significant interest for exploration as an antitumor approach in melanoma, as members of the BRAF signaling pathway are client proteins and are implicated in the majority of melanomas," said Dr. Kefford. "These very early data with tanespimycin demonstrate tolerability in this advanced metastatic melanoma patient population. The conditions have been fulfilled for expanded patient accrual in this Phase 2 trial to further explore efficacy."
"Metastatic melanoma is the fourth cancer indication in which a Kosan Hsp90 inhibitor has demonstrated antitumor activity and a high degree of tolerability, providing additional proof-of-concept that Hsp90 inhibition has applicability in a broad range of tumor types and that our lead Hsp90 inhibitor, tanespimycin, has significant therapeutic potential," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "Tanespimycin will be the first Hsp90 inhibitor to enter registration trials and has the potential to be the first Hsp90 inhibitor to reach the market. Our TIME registration program for tanespimycin in patients with multiple myeloma is on track to be initiated in the third quarter of 2007, which will be a major milestone for our company."
Phase 2 Tanespimycin Melanoma Trial
Tanespimycin binds to and inhibits the activity of Hsp90. Hsp90 inhibition results in the degradation of a variety of RAF family proteins, including mutant BRAF. As the majority of melanomas have activation of the BRAF-MAP kinase pathway, it is postulated that tanespimycin interrupts the MAP kinase pathway and may lead to clinically significant anti-melanoma effects. The Phase 2 trial of tanespimycin was designed as a multi-center two-stage Simon design study; continuation to the second stage required at least 1 of the first 9 patients to have a progression-free survival (PFS) time of at least 24 weeks, the primary endpoint of the trial. Eligible patients had stage M1 melanoma, measurable/unresectable disease and had progressed within 3 months of study entry with no more than 1 prior chemotherapy treatment for metastatic melanoma. Tanespimycin was administered at a dose of 275 mg/m2 by 1-2 hour intravenous infusion 2 times per week every 2 out of 3 weeks until disease progression or toxicity. 20 patients have been enrolled, and efficacy data are available on 14 evaluable patients. One of the 6 evaluable patients with a BRAF mutation (V600E) showed evidence of anti-melanoma activity. An additional patient with BRAF mutation continues on study but is too early to assess for efficacy at present. The safety profile has been manageable and included predominantly Grade 1 and 2 toxicities (constitutional and gastrointestinal symptoms). Grade 3 or 4 toxicity, which was generally manageable and reversible, resulted in treatment discontinuation in 2 patients. Accrual is continuing toward the goal of enrolling a total of 30 evaluable patients (with continued BRAF mutation analysis). |
