Description and Target

Tucatinib was added to our pipeline in March 2018 with the acquisition of Cascadian Therapeutics. It is an orally bioavailable, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2, a growth factor receptor that is over-expressed in multiple cancers, including breast, colorectal, esophageal, gastric, lung and ovarian cancers. It is over-expressed in approximately 20% of breast cancers.

Tucatinib has been evaluated as a single agent and in combination with both chemotherapy and other HER2-directed agents including Herceptin® (trastuzumab) and Kadcyla® (trastuzumab emtansine). Results from phase 1b trials showed that the combination of tucatinib, capecitabine and trastuzumab was generally well-tolerated and demonstrated clinical activity in patients with and without brain metastases.

Clinical Development Status

  • HER2CLIMB: A randomized, double-blind, controlled phase 2 pivotal clinical trial comparing tucatinib versus placebo, each in combination with capecitabine (Xeloda®) and trastuzumab (Herceptin®), for patients with locally advanced or metastatic HER2+ breast cancer who have had prior treatment with a taxane, trastuzumab, pertuzumab (Perjeta®) and Kadcyla® (ado-trastuzumab emtansine or T-DM1) and who may or may not have brain metastases

  • Tucatinib is also being studied in investigator-sponsored trials in earlier lines of metastatic breast cancer treatment and in HER2+ colorectal cancer