Tucatinib Developer Seeks FDA Approval for the Treatment of HER2-Positive Breast Cancer

Tucatinib developer, Seattle Genetics, Inc., has submitted a new drug application to the FDA for tucatinib in combination with trastuzumab (Herceptin) and capecitabine for the treatment of patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, who have received at least 3 prior HER2-directed drugs alone or in combination with other drugs, in the neoadjuvant, adjuvant, or metastatic setting, according to a press release.¹

“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,” said Roger Dansey, MD, chief medical officer at Seattle Genetics. “We look forward to working with the FDA on the review of this application.”

The NDA followsBreakthrough Therapy designation from the FDA for tucatinibin combination with trastuzumab and capecitabine for the treatment of patients within this population, which was based on the results from the HER2CLIMB trial. Data from the HER2CLIMB trial were recently published in theNew England Journal of Medicine.

As previously reported byTargeted Oncology, the HER2CLIMB study demonstrated a 46% decrease in risk of disease progression or death in patients with the tucatinib combination versus placebo in patients with locally advanced unresectable or metastatic HER2-positive breast cancer (HR 0.54; 95% CI, 0.42-0.71;P< .00001), meeting its primary end point of improvement in progression-free survival (PFS).&nbsp;²

The combination of tucatinib, trastuzumab, and capecitabine was also found to be tolerable among study participants, with only 223 grade 3 or higher adverse events (AEs) occurring the tucatinib arm (n = 410). Additionally, the rate of grade 3 or higher AEs was similar between the tucatinib arm and the placebo arm at 55.2% and 48.7%, respectively. The most common adverse events in the tucatinib group versus the placebo group were diarrhea (80.9% vs 53.3 %), Palmar-Plantar erythrodysesthesia syndrome (63.4 % vs 52.8%), nausea (58.4 % vs 43.7%), fatigue (45.0% vs 43.1%), and vomiting (35.9 % vs 25.4 %), respectively.³

Secondary end points of the study included PFS in patients with baseline metastases, overall survival, PFS based on investigator assessment per RECIST 1.1. criteria, objective response rate, duration of response, clinical benefit rate, the incidence of AEs, the incidence of health resources utilization, quality of life, and pharmacokinetics. &nbsp;

Tucatinib is an investigational orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. The drug is also being studied in combination with trastuzumab in the multi-center, open-label, single-arm phase II MOUNTAINEER trial, which is evaluating the combination in patients with HER2-positive,RASwild-type, metastatic or unresectable colorectal cancer.

Tucatinib is the first investigational therapy in a pivotal trial to address the unmet need for patients with metastatic HER2-positive breast cancer with or without brain metastases, according to Seattle Genetics.

References

1. Seattle Genetics Announces Submission of Tucatinib New Drug Application to the U.S. FDA for Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer [news release]. Bothell, Washington: Seattle Genetics, Inc; December 23, 2019. https://bit.ly/2PNL1ue. Accessed December 23, 2019.
2. Seattle Genetics Announces Positive Topline Results from Pivotal Trial of Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer [news release]. Bothell, Washington: Seattle Genetics; October 21, 2019. bit.ly/2M9ImZx. Accessed December 18, 2019.
3. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer.N Engl J Med. 2019. doi: 10.1056/NEJMoa1914609.