Seagen Inc. announced data from the Phase 3 HER2CLIMB-02 clinical trial of TUKYSA (tucatinib) in combination with the antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla). The combination showed a statistically significant improvement in progression-free survival (PFS), the study's primary endpoint, in patients with unresectable locally advanced or metastatic human epidermal growth factor receptor 2-positive (HER2-positive) breast cancer who had been previously treated with trastuzumab and a taxane, compared to those who received placebo plus ado-trastuzumib emtansine. Discontinuations due to adverse events were more common in the combination arm of the trial, but no new safety signals were observed for the combination.

Patients who received TUKYSA in combination with ado-trastuzum AB emtansine experienced: Median PFS of 9.5 months (95% Confidence Interval [CI]: 7.4, 10.9) by investigator assessment per RECIST v1.1 compared to 7.4 months (95% CI: 5.6, 8.1) in the placebo plus ado-trastizumab emtansine arm (Hazard Ratio [HR], 0.76 [95% CI: 0.61, 0.95); P=0.0163). The most common (5%) Grade 3 or higher adverse events (AEs) were alanine transferase (ALT) increase (16.5% versus 2.6%), aspartate transferase (AST) increase (16.5%. anemia (8.2% versus 4.7%), thrombocytopenia (7.4% versus 2.1%), and fatigue (6.1% versus 3.0%).

TUKYSA in combination With trastuzumab and capecitabine is approved by the U.S. Food and Drug Administration (FDA) based on the results of the HER2CLIMB trial and is the only Category 1 preferred recommendation by the National Comprehensive Cancer Network for third-line metastatic HER2-positive breast cancer.