Kosan's Hsp90 Inhibitor, Tanespimycin, Shows Promising Antitumor Activity in Phase 2 Trial of Patients with HER2-Positive Metastatic Breast Cancer
Thursday December 14, 11:31 am ET
HAYWARD, Calif., Dec. 14 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) today presented preliminary data from a Phase 2 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.
"The demonstration of clinical benefit with tanespimycin combined with trastuzumab, in patients with trastuzumab-refractory HER2-positive metastatic breast cancer, is quite promising," said Dr. Hudis. "The encouraging evidence of tolerability and activity from this Phase 2 trial strongly support the continued development of an Hsp90 inhibitor as a potential treatment for patients with breast cancer whose disease has proven to be resistant to conventional therapy."
"We believe that these favorable Phase 2 results with tanespimycin, our first-generation Hsp90 inhibitor, establish an important proof-of-concept for Hsp90 inhibition in the treatment of breast cancer and set the stage for advancing into later-stage trials," said Robert G. Johnson, Jr., M.D., Ph.D., President and Chief Executive Officer of Kosan. "We believe that our second-generation Hsp90 inhibitor, alvespimycin HCl, is optimally suited for further development in breast cancer due to its enhanced pharmaceutical properties including greater potency, longer half-life, ease of formulation and oral bioavailability. A Phase 1/2 trial of alvespimycin in combination with trastuzumab is ongoing and we plan to initiate later-stage trials with alvespimycin in patients with HER2-positive metastatic breast cancer in the first half of 2007. We will continue to develop tanespimycin on a registration path as a treatment for multiple myeloma where the compound has demonstrated promising clinical activity to date."
Phase 2 Tanespimycin Results
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 2 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).
* One patient with documented progressive disease in the liver prior to study while being treated with trastuzumab/vinorelbine had a confirmed partial response (53% tumor shrinkage by RECIST) and continues on study (Cycle 9+);
* One patient with documented progressive disease on study for one year post-trastuzumab treatment had an unconfirmed partial response (35% tumor shrinkage by RECIST) and continues on study (Cycle 3+); and
* Three patients who received 4-6+ cycles of treatment had stable disease; one with a 20% decrease in measurable disease.
The tanespimycin plus trastuzumab regimen was generally well tolerated. Grade 1 and 2 toxicities included fatigue, diarrhea, nausea, vomiting, and Grade 3 toxicity was seen in 3 patients (2 patients with headache, 1 patient with fatigue), all of which were manageable and reversible.
Future Development Plans
Kosan plans to initiate further trials in HER2-positive metastatic breast cancer using alvespimycin HCl (KOS-1022), a second-generation Hsp90 inhibitor. Alvespimycin has enhanced pharmaceutical properties: longer half-life that allows more flexible dosing; increased potency, enabling potentially lower dosing; good oral bioavailability, and water solubility, enabling ease of formulation. Alvespimycin is currently being tested in several clinical trials: Phase 1b (intravenous formulation) in combination with trastuzumab in HER2+ metastatic breast cancer; Phase 1 (oral formulation), as a single agent in solid tumors; and Phase 1 (intravenous formulation) as a single agent in hematological tumors. The compound has demonstrated promising clinical results to date. Kosan anticipates initiating a Phase 2 trial of alvespimycin as a single agent in HER2-positive metastatic breast cancer in the first half of 2007, with subsequent Phase 2/3 trials in HER2-positive metastatic breast cancer in combination with trastuzumab. |
