There are multiple cohorts in this trial:~5 tumor specific cohorts with HER2 overexpression/amplification (cervical cancer, uterine cancer, biliary tract cancer, urothelial cancer, and non-squamous non-small cell lung cancer [NSCLC])~2 tumor specific cohorts with HER2 mutations (non-squamous NSCLC and breast cancer)~2 cohorts which will enroll all other HER2 amplified/overexpressed solid tumor types (except breast cancer, gastric or gastroesophageal junction adenocarcinoma [GEC], and colorectal cancer [CRC]) or HER2-mutated solid tumor types.
This trial studies how well tucatinib works for solid tumors that make either more HER2 or a different type of HER2 than usual (HER2 alterations) The solid tumors studied in this trial have either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable).~All participants will get both tucatinib and trastuzumab. People with hormone-receptor positive breast cancer will also get a drug called fulvestrant.~The trial will also look at what side effects happen. A side effect is anything a drug does besides treating cancer.