A phase 2 basket study of tucatinib and trastuzumab in solid tumors with human epidermal growth factor receptor 2 alterations: Uterine and cervical cancer cohorts (SGNTUC-019, trial in progress)

Tucatinib, a highly selective human epidermal growth factor receptor 2 (HER2)-directed tyrosine kinase inhibitor, is approved in combination with trastuzumab and capecitabine in multiple regions for HER2-positive (HER2+) metastatic breast cancer. Tucatinib is being further investigated in combination with trastuzumab in HER2+ cancers and cancers with HER2 mutations, including locally-advanced unresectable or metastatic (LA/M) HER2+ cervical and uterine cancers. The prognoses of LA/M cervical and uterine cancers remain poor, with HER2 overexpression/amplification occurring in 0.5–21% of cervical cancers and 4–80% of uterine cancers. In xenograft models of HER2+ and HER2-mutated tumors, dual targeting with tucatinib and trastuzumab showed superior activity to either agent alone. SGNTUC-019 (NCT04579380) is an open-label, international, phase II, basket study evaluating tucatinib and trastuzumab in adult patients with LA/M HER2+ or HER2-mutated solid tumors.