FDA Grants Breakthrough Therapy Designation for Tucatinib in HER2-Positive Breast Cancer

The FDA granted breakthrough therapy designation to tucatinib in combination with trastuzumab (Herceptin) and capecitabine (Xeloda) for locally advanced or metastatic HER2-positive breast cancer, Seattle Genetics, Inc. announced.¹

This development comes on the heels of an announcement of the HER2CLIMB clinical trial’s results in October 2019, and further data being presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) on December 11. The results were also published in the New England Journal of Medicine.

“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, MD, Chief Medical Officer at Seattle Genetics, in a press release.

This new combination including tucatinib to treat HER2-positive breast cancer met its primary endpoint of progression-free survival (PFS) with a 46% reduction in disease progression or death (hazard ratio [HR], 0.54; 95% CI, 0.42-0.71; P< .00001). Median PFS was 7.8 months (95% CI, 7.5-9.6) for the new combination, compared to 5.6 months (95% CI, 4.2, 7.1) in the control arm.²

Tucatinib is a tyrosine kinase inhibitor (TKI) that is highly selective for HER2. It improved overall survival (OS) with a 34% reduction in the risk of death (HR, 0.66; 95% CI, 0.50-0.88; P= 0.0048), and demonstrated an improved PFS for patients with brain metastases at base-line, with a 52% reduction in the risk of disease progression or death (HR, 0.48; 95% CI, 0.34-0.69; P< .00001).

The new combination was well-tolerated among patients, according to the data. The most common adverse events seen in treatment included diarrhea, palmar-plantar erythrodysaesthesia syndrome (PPE), nausea, fatigue, and vomiting. The percent of patients who requested to stop treatment was 5.7% compared to 3% in the control arm.

The FDA’s breakthrough therapy process is designed to expedite the review of potential new therapies, given the clinical trial’s evidence shows substantial data for the ability of improvement over existing therapies. In this case, the addition of tucatinib with trastuzumab and capecitabine warranted just that.

“We intend to submit a New Drug Application to the FDA and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) by the first quarter 2020, with the goal of making tucatinib available to patients in this setting as soon as possible,” said Dansey in the press release.

References:

1. Seattle Genetics Announces U.S. FDA Grants Breakthrough Therapy Designation for Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer [news release]. Seattle Genetics. Bothell, Washington. Published December 18. https://investor.seattlegenetics.com/press-releases/news-details/2019/Seattle-Genetics-Announces-US-FDA-Grants-Breakthrough-Therapy-Designation-for-Tucatinib-in-Locally-Advanced-or-Metastatic-HER2-Positive-Breast-Cancer/default.aspx. Accessed December 18.

2. Seattle Genetics Announces Positive Tucatinib HER2CLIMB Trial Results in Locally Advanced or Metastatic HER2-Positive Breast Cancer Presented at 2019 SABCS and Published in the New England Journal of Medicine [news release]. Seattle Genetics. Bothell, Washington. Published December 11. https://investor.seattlegenetics.com/press-releases/news-details/2019/Seattle-Genetics-Announces-Positive-Tucatinib-HER2CLIMB-Trial-Results-in-Locally-Advanced-or-Metastatic-HER2-Positive-Breast-Cancer-Presented-at-2019-SABCS-and-Published-in-the-New-England-Journal-of-Medicine/default.aspx. Accessed December 18.