Our lead development candidate, tucatinib (also known as ONT-380), is an investigational, oral bioavailable, potent tyrosine kinase inhibitor (TKI) that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including diarrhea and skin rash. HER2 is a growth factor receptor that is over-expressed in approximately 20% of breast cancers.
We are currently conducting a randomized (2:1), double-blind, controlled pivotal clinical trial, known as HER2CLIMB, 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. Please visit HER2CLIMB.com or ClinicalTrials.gov for more information.
Our two Phase 1b trials of tucatinib, one in combination with T-DM1 and another in combination with capecitabine and/or trastuzumab, are fully enrolled and patients remain on treatment. Results from the Phase 1b trials indicate these drug combinations are well tolerated and may provide clinical activity in heavily pretreated patients with metastatic breast cancer, with and without brain metastases. In addition, our strategy is to evaluate tucatinib through investigator-sponsored trials in combination with approved agents in other HER2-expressing cancers or earlier in the metastatic breast cancer treatment paradigm.