(UroToday.com) Tucatinib is a highly selective HER2-directed tyrosine-kinase inhibitor recently approved for HER2 overexpressed/amplified (HER2+) metastatic breast cancer and is being developed as a novel therapy for patients with metastatic colorectal cancer, gastric cancer, and other gastrointestinal tumors. In xenograft models of HER2+ and HER2-mutated tumors, dual targeting of HER2 with tucatinib and trastuzumab showed superior activity to either agent alone. Despite the development of several new therapies for metastatic urothelial cancer, response durations generally remain short and the great majority of patients succumb to the disease, highlighting the need for therapeutic approaches. Given that 20-30% of urothelial cancers have molecular alterations of the ErbB family, tucatinib in combination with trastuzumab warrants further evaluation in this population.

The SGNTUC-019 basket study is evaluating tucatinib in combination with trastuzumab in patients with HER2+ or HER2-mutated solid tumors, including a cohort of patients with locally advanced or metastatic urothelial cancer. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Evan Yu and colleagues presented the study design for SGNTUC-019.

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