NEW YORK – Seattle Genetics said Wednesday that its Phase II HER2CLIMB trial for tucatinib in treating HER2-positive metastatic breast cancer yielded positive data. The results were presented at the 2019 San Antonio Breast Cancer Symposium and the accompanying study was published in the New England Journal of Medicine.
The randomized, 612-patient trial evaluated the effects of tucatinib and chemotherapy versus chemotherapy alone for unresectable locally advanced or metastatic HER2-positive breast cancer. Enrolled patients have been previously treated with chemotherapy and HER2-targeted compounds. Almost half of the patient cohort had brain metastases at the time of enrollment.
Tucatinib is an orally administered small-molecule tyrosine kinase inhibitor of the human epidermal growth factor receptor 2 (HER2). Because tucatinib is highly selective for HER2, it does not significantly inhibit EGFR. Patients who are HER2-positive have high levels of the protein HER2 on their tumors, which could aid in the spread of cancer cells.
In evaluating the first 480 patients enrolled in the trial, investigators found that tucatinib increased progression-free survival, the primary endpoint for the trial. At the one-year mark, 33.1 percent of patients who received the tucatinib combination had progression-free survival compared to 12.3 percent for patients who only received the chemotherapy combination. Tucatinib also improved the duration of progression-free survival (7.8 months versus 5.6 months).
Overall survival at two years was 44.9 percent for the tucatinib group and 26.6 percent for the chemotherapy group.
In 2017, tucatinib was granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.
"Tucatinib demonstrated a statistically significant and clinically meaningful benefit in overall survival, progression-free survival and objective response rate compared to the control arm," Seattle Genetics CMO Roger Dansey said in a statement. "We plan to submit a New Drug Application (NDA) to the US Food and Drug Administration and a Marketing Authorization Application (MAA) to the European Medicines Agency by the first quarter of 2020, with the goal of bringing a much-needed new medicine to patients."