- Designation Based on Positive Pivotal HER2CLIMB Trial Evaluating Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer; Data were Presented at 2019 SABCS and Published in the New England Journal of Medicine -

- New Drug Application Submission to U.S. FDA Expected by First Quarter of 2020 -

BOTHELL, Wash.--(BUSINESS WIRE)-- Seattle Genetics, Inc. (Nasdaq:SGEN) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to tucatinib, in combination with trastuzumab and capecitabine, for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. The positive topline results of the pivotal HER2CLIMB clinical trial were announced in October 2019, and additional data were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 11, 2019 and were simultaneously published in the New England Journal of Medicine (NEJM). Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

The FDA’s Breakthrough Therapy process is intended to expedite the development and review of promising drug candidates intended for serious or life-threatening conditions. Designation is based upon preliminary clinical evidence of the potential for substantial improvement over existing therapies on one or more clinically significant endpoints.

“The addition of tucatinib to the commonly used combination of trastuzumab and capecitabine demonstrated superior activity compared to trastuzumab and capecitabine alone in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “The decision by the FDA to grant Breakthrough Therapy designation to tucatinib recognizes the urgent need for new medicines that can impact the lives of those with HER2-positive metastatic breast cancer. We intend to submit a New Drug Application to the FDA and an MAA to the EMA by the first quarter 2020, with the goal of making tucatinib available to patients in this setting as soon as possible.”

This Breakthrough Therapy designation was based on data from the pivotal HER2CLIMB clinical trial, which compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients had received a median of four prior lines of therapy overall and three in the metastatic setting. Forty-seven percent of the patients enrolled in the trial had brain metastases at the time of enrollment.

Data presented at SABCS and published in NEJM include the primary endpoint of progression-free survival (PFS) as assessed by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. The primary endpoint of PFS showed that the addition of tucatinib was superior to trastuzumab and capecitabine alone, with a 46 percent reduction in the risk of disease progression or death (hazard ratio (HR)=0.54 (95% Confidence Interval (CI): 0.42, 0.71); p