Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations

Inclusion Criteria

Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available
Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease
Disease progression during or after, or intolerance of, the most recent line of systemic therapy

Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory, according to one of the following:

HER2 overexpression/amplification from fresh or archival tumor tissue or blood
Known activating HER2 mutations detected in fresh or archival tumor tissue or blood
Have measurable disease per RECIST v1.1 criteria according to investigator assessment
Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria

Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial.

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.