Kosan's Hsp90 Inhibitor, Tanespimycin, Shows 55% Clinical Benefit in Patients With Trastuzumab-Refractory Metastatic Breast Cancer
Monday December 17, 6:00 am ET
[These results look better than I expected. Maybe they will even give the share price something of a boost].
Five of 20 Evaluable Patients Had Confirmed Partial Responses (25%); Updated Data Presented at San Antonio Breast Cancer Symposium
HAYWARD, Calif., Dec. 17 /PRNewswire-FirstCall/ -- Kosan Biosciences Incorporated (Nasdaq: KOSN - News) today announced that its Hsp90 inhibitor, tanespimycin, demonstrated meaningful antitumor activity and tolerability in a Phase 2 trial in patients with HER2-positive metastatic breast cancer, when administered in combination with trastuzumab (Herceptin®) in patients whose disease progressed following treatment with trastuzumab immediately prior to entering the trial. Of 20 evaluable patients, 11 patients benefited from activity, yielding an overall clinical benefit incidence of 55%, including 5 patients with confirmed partial responses, 2 patients with minor responses and 4 patients with extended stable disease. Common toxicities were mainly mild to moderate and included fatigue and gastrointestinal symptoms. Data from the Phase 2 trial were presented at the 2007 San Antonio Breast Cancer Symposium on Sunday, December 16, 2007, in a poster titled, "Tanespimycin (an Hsp90 Inhibitor) and Trastuzumab is an Active Combination in Patients (Pts) with HER2-Positive Trastuzumab-Refractory Metastatic Breast Cancer (MBC): Phase 2 Trial," by Shanu Modi, M.D., of Memorial Sloan-Kettering Cancer Center.
"Tanespimycin is clearly active in patients who are refractory to trastuzumab and whose disease progressed prior to entering the study," said Clifford A. Hudis, M.D., Chief, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, and senior author on the poster. "The tolerability of tanespimycin combined with the ability to generate meaningful and durable responses, including a large number of partial responses, in this patient population supports the development of Hsp90 inhibition in the treatment of HER2-positive metastatic breast cancer and underscores the therapeutic potential of tanespimycin in this indication. These data confirm and extend the activity seen in the Phase 1 trial, described in our recent publication in the Journal of Clinical Oncology, and we are pleased to see this drug candidate continuing to deliver clinical benefit and advancing in the clinic."
"The data in this Phase 2 trial continue to strengthen as we have added patients," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "We believe that tanespimycin is highly active in patients with HER2-positive metastatic breast cancer who have progressed on trastuzumab, and that this drug candidate's overall profile is attractive. We intend to complete this Phase 2 trial and embark upon next steps to explore tanespimycin's therapeutic potential in breast cancer."
Phase 2 Tanespimycin Data
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 objective of the Phase 2 trial is to determine the objective response rate by RECIST in patients with HER2-positive metastatic breast cancer. To be eligible for the trial, patients may have had either progressive disease within 3 months following last dose of adjuvant treatment with trastuzumab or have progressive disease following initial therapy for metastatic disease with trastuzumab (trastuzumab may have been administered with cytotoxic chemotherapy or as a single agent). All but one patient received trastuzumab in the metastatic setting (one patient received trastuzumab only in the adjuvant setting). Tanespimycin was administered at a dose of 450 mg/m2 following administration of the standard dose of trastuzumab.
Of 26 patients enrolled in the trial, 20 were evaluable for efficacy (3 patients were not evaluable for efficacy and 3 patients are too early to assess). Of the 26 patients enrolled, 21 were treated with Kosan's prior Cremophor®-containing injection formulation of tanespimycin (4 of whom were crossed over to receive the recently introduced Injectable Suspension formulation), and 5 were treated with the Injectable Suspension formulation (3 of whom were recently enrolled and are not yet evaluable). Of the 20 patients evaluable for efficacy, 11 responded, yielding a clinical benefit rate of 55%.
-- 5 patients experienced confirmed partial responses, including,
-- 1 patient with 75% decrease in liver metastases with 42% drop in CEA; 8 months on study;
-- 1 patient with 45% decrease in a hilar node, continuing on study after 14 months;
-- 1 patient with 33% decrease in right breast lesions with decreased tumor markers, continuing on study after 7 months;
-- 1 patient with 57% decrease in lymph nodes, liver and left breast lesions, continuing on study after 7 months; and
-- 1 patient with 37% decrease in lymph nodes, continuing on study after 5 months.
-- 2 patients experienced minor responses with decreased tumor markers (on study for 6 and 5 months).
-- 4 patients had stable disease for 4, 4, 7, and 8 months.
Common toxicities were mainly Grade 1 and 2 and included diarrhea, fatigue, dizziness and headache. Treatment-related Grade 3 toxicities were experienced by 3 patients and included reversible fatigue and headache, increased liver function tests that resolved in 9 days and unsteady gait and euphoric mood that resolved in a single day. Noticeably absent were toxicities associated with conventional chemotherapy, including alopecia, myelosuppression, cardiotoxicity and peripheral neuropathy.
Accrual is continuing in this Phase 2 trial. Up to 20 additional patients are anticipated to be treated with the Injectable Suspension formulation of tanespimycin. |
