Kosan Initiates Trial Of Alvespimycin In HER2-Positive Metastatic Breast Cancer
Kosan Biosciences initiates Phase 2 trial of alvespimycin, the company's second-generation Hsp90 inhibitor, in patients with HER2-positive metastatic breast cancer.
Alvespimycin has demonstrated the potential to disrupt the activity of multiple oncogenes and cell signaling pathways implicated in tumor growth, including HER2, a key signaling pathway in breast cancer. The objective of the Phase 2 trial is to evaluate the safety and anticancer activity of alvespimycin as a single agent in patients who have not previously received Herceptin for metastatic disease except in an adjuvant setting. Antitumor data in patients with advanced HER2-positive cancer presented at the September 2007 American Society of Oncology (ASCO) Breast Cancer Symposium demonstrated encouraging antitumor activity of alvespimycin in combination with trastuzumab (Herceptin).
"HER2-positive metastatic breast cancer represents a major market opportunity for Kosan that we intend to pursue," said Robert G. Johnson, Jr., M.D., Ph.D., Kosan's President and Chief Executive Officer. "We believe that emerging safety and efficacy data from our clinical trials in this indication with both of our Hsp90 inhibitors and the demonstrated activity in refractory disease represent a meaningful therapeutic opportunity. We believe that characterization of the single-agent activity of an Hsp90 inhibitor in HER2-positive metastatic breast cancer will provide valuable information to support the design of later-stage trials."
Alvespimycin Phase 2 Development Plan
The single-agent trial of alvespimycin will be conducted in Eastern Europe and will recruit up to 30 patients in a two-stage trial design. Patients with HER2-positive metastatic disease and no prior trastuzumab treatment except as adjuvant therapy (with the last dose more than 12 months prior to study entry) are eligible to participate in the trial. Alvespimycin will be administered intravenously on a one-hour weekly infusion schedule of 80 mg/m2 for three weeks out of four weeks in repeated cycles.
Kosan is also testing alvespimycin delivered orally in a Phase 1 dose escalation trial exploring different schedules.
Promising Antitumor Activity Shown in Phase 1
In September, at the 2007 ASCO Breast Cancer Symposium, Kosan reported that alvespimycin demonstrated promising antitumor activity and tolerability in combination with trastuzumab in a Phase 1 trial of patients with refractory HER2-positive metastatic breast cancer, and in patients with refractory ovarian cancer who were progressing on standard chemotherapy. Of the 27 heavily-pretreated patients enrolled in the Phase 1 trial, 24 patients had HER2-positive metastatic breast cancer and 3 patients had ovarian cancer (HER2 status unknown).
Clinical benefit was observed in 42% of patients (8 of 19 evaluable) with HER2-positive metastatic breast cancer. Of the 3 patients with ovarian cancer, 1 patient (13 prior regimens) who was on study for more than 16 months had a near complete resolution of ascites and left pleural effusion, and an 83% decrease in CA125. Toxicities in this Phase 1 trial were mainly Grade 1 and 2 (diarrhea, fatigue, headache, arthralgia, nausea) with 80 mg/m2 established as the recommended Phase 2 dose for weekly intravenous administration. Kosan is currently enrolling a Phase 1 trial to investigate alvespimycin plus trastuzumab and paclitaxel to establish the initial safety profile and pharmacokinetics of this triplet regimen and to lay the groundwork for a potential larger Phase 2/3 trial.