Efficacy results of first targeted therapy for HER2+ mCRC

Tukysa (tucatinib) is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein, a protein that contributes to cancer cell growth. HER2 is overexpressed in multiple cancers, including colorectal cancers. Tukysa in combination with trastuzumab and capecitabine was approved by the US FDA in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases. Awaiting the response on the NDA submitted to US FDA in July 2022, Seagen will be presenting updated results for its potentially first targeted therapy for HER2+ mCRC at the EMSO 2022 – MOUNTAINEER trial. In July 2022, Seagen presented positive results from the pivotal Phase II MOUNTAINEER trial investigating TUKYSA in combination with trastuzumab in patients with previously treated HER2+ mCRC at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer.

In combination with trastuzumab, tucatinib appears to be a promising therapy demonstrating a 38.1% confirmed response rate. Further making a case for itself, the drug has given mOS, mPFS, and DOR of 24.1 months, 8.2 months, and 12.4 months, respectively. Based on these results, the US FDA granted TUKYSA Breakthrough Therapy Designation. From being identified as a negative predictive factor to becoming a positive, actionable target, multiple pharma companies have been trying to target HER2+ mCRC patients, and there are now a plethora of HER2-targeted therapies in clinical trials. The approval of Tukysa will open a new personalized treatment approach in mCRC, a leading cause of cancer-related mortality despite great advances in treatment over the years.