Seattle Genetics has announced plans to file its breast cancer drug tucatinib after the drug met targets in a heavily pre-treated group of patients with advanced disease.
The HER2CLIMB trial compared tucatinib combined with trastuzumab and capecitabine, with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer.
Patients had previously received Roche’s drugs Herceptin (trastuzumab), Perjeta (trastuzumab) and Kadcyla (ado-trastuzumab emtansine) and 47% of those on the trial had brain metastases at the time of enrolment.
Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.
The trial met the primary endpoint of progression-free survival (PFS), showing that the addition of tucatinib was superior to trastuzumab and capecitabine alone, with a 46% reduction in the risk of disease progression or death.
The tucatinib arm demonstrated an improvement in overall survival, with a 34% reduction in the risk of death compared to trastuzumab and capecitabine alone.
For patients with brain metastases at baseline, the tucatinib arm also demonstrated superior PFS, with a 52% reduction in the risk of disease progression or death compared to those who received trastuzumab and capecitabine alone.
The tucatinib combination was generally well tolerated with a manageable safety profile, the company said, with the most frequent adverse events in the tucatinib arm including diarrhoea, palmar-plantar erythrodysesthesia syndrome (PPE), nausea, fatigue, and vomiting.
Grade 3 or greater adverse events in the tucatinib arm compared to the control arm included diarrhoea (12.9% vs. 8.6%), increased aspartate aminotransferase (AST) (4.5% vs. 0.5%), increased alanine aminotransferase (ALT) (5.4% vs. 0.5%) and increased bilirubin (0.7% vs. 2.5%).
There was no requirement for prophylactic antidiarrheals. Adverse events leading to discontinuations were infrequent in both the tucatinib arm and the control arm at 5.7% and 3%, respectively.
Seattle Genetics’ chief medical officer, Roger Dansey, said the company plans to file results with the FDA in the first quarter of 2020.