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Kosan Hsp90 Inhibitor Shows Anti-tumor Activity


Posted on 2006-12-14 11:29:00



Kosan Biosciences Incorporated today presented preliminary data from a Phase II clinical trial showing that tanespimycin (KOS-953) in combination with trastuzumab (Herceptin) demonstrated clinically meaningful antitumor activity, including both partial responses and extended stabilization of disease, in patients with trastuzumab-refractory HER2-positive metastatic breast cancer.

Preliminary data from the ongoing trial were presented in a poster at the 29th Annual San Antonio Breast Cancer Symposium. The poster was entitled, "Phase 2 trial of Trastuzumab (T) and KOS-953 (17-AAG) in Patients (pts) with HER2-Positive Breast Cancer: Preliminary Results," and was presented by Shanu Modi, M.D., Breast Cancer Medicine Service, Memorial Sloan- Kettering Cancer Center. Clifford A. Hudis, M.D., Chief, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, was the senior author on the study.

Tanespimycin is an Hsp90 inhibitor that has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key pathway in breast cancer.

The Phase II trial of tanespimycin in combination with trastuzumab was designed to determine the objective response rate by RECIST in patients with HER2-positive metastatic breast cancer with tumor progression during treatment with one trastuzumab-containing regimen immediately prior to entering the trial. The dosing schedule for tanespimycin was a two-hour weekly intravenous infusion of 450 mg/m2 administered along with the standard dose of trastuzumab. Of the 12 patients enrolled in the trial, all had one prior trastuzumab containing regimen, and many patients had been heavily pre-treated with additional non-trastuzumab-based cytotoxic chemotherapy. Patients had a median of three prior cytotoxic regimens and four patients had received prior hormonal therapy.

Of the eight patients evaluable for efficacy, five (63%) showed signs of clinical benefit (one patient with stable disease was still active in Cycle 3 and was too early to assess for efficacy).


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