Drugmaker Seattle Genetics is seeking regulatory approval for a small-molecule drug designed to treat a common form of breast cancer.
The Bothell, Washington-based biotech company said Monday that it had submitted its application to the Food and Drug Administration for tucatinib for patients with locally advanced unresectable or metastatic breast cancer with HER2 genetic mutations who have received at least three prior HER2-directed drugs. The drug would be combined with Roche’s Herceptin (trastuzumab) and the chemotherapy drug capecitabine.
The submission is based on results of the Phase II HER2CLIMB trial, for which the company announced positive results in October. Seattle Genetics took control of tucatinib when it acquired Seattle-based Cascadian Therapeutics for $614 million in January 2018. The news came the same day that the FDA gave accelerated approval to AstraZeneca and Daiichi Sankyo’s Enhertu (fam-trastuzumab deruxtecan), a HER2-targeting antibody-drug conjugate that itself is the subject of a legal dispute between Seattle Genetics and Daiichi Sankyo.
“Today’s submission marks another important milestone for Seattle Genetics and tucatinib and a potential advance for patients with either locally advanced or metastatic HER2-positive breast cancer, including those with and without brain metastases,” Seattle Genetics Chief Medical Officer Roger Dansey said in a statement. “We look forward to working with the FDA on the review of this application.”
The FDA gave tucatinib Breakthrough Therapy designation last week, following the presentation of data from HER2CLIMB at the San Antonio Breast Cancer Symposium and its publication in the New England Journal of Medicine.
Data from HER2CLIMB on 480 patients presented at the SABCS conference showed a median progression-free survival (PFS) of 7.8 months for the combination of tucatinib, Herceptin and capecitabine, compared with 5.6 months for Herceptin and capecitabine alone. Estimated PFS at one year was 33% in the tucatinib arm, compared with 12% in the control arm, and data indicated that adding tucatinib reduced the risk of progression or death by 46%. There was also an improvement on the secondary endpoint of overall survival (OS), with the tucatinib and control arms respectively showing a median OS of 21.9 months and 17.4 months. Median OS at two years was 45% for patients on tucatinib, compared with 27% in the control arm. Those data meant a 34% reduction in the risk of death for patients on tucatinib. Improvements in PFS were also seen among patients whose cancer had metastasized to the brain. The drug was also well-tolerated, with study results showing a low discontinuation rate due to adverse events.
If approved, tucatinib would become the third Seattle Genetics drug to hit the market, after the blood cancer drug Adcetris (brentuximab vedotin) and the bladder cancer drug Padcev (enfortumab vedotin-ejfv).
Photo: Donald Miralle, Getty Images
