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

Trial Status: Active

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.

Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
  • Participants with disease types other than breast cancer, biliary tract cancer, non-squamous NSCLC, and cervical cancer: Disease progression on or after the most recent systemic therapy for locally-advanced unresectable or metastatic disease
  • Participants with any breast cancer subtype:
  • Must have HER2-mutated disease which does not display HER2 overexpression/amplification
  • Must have progressed on or after ≥1 prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy) for locally-advanced unresectable or metastatic breast cancer
  • Participants with metastatic HR+ HER2-mutated disease must have received a prior CDK4/6 inhibitor in the metastatic setting.
  • Participants with biliary tract cancer: must have completed ≥1 prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy)
  • Participants with non-squamous NSCLC: has relapsed from or is refractory to standard treatment or for which no standard treatment is available
  • Participants with cervical cancer:
  • Participants with metastatic cervical cancer must have progressed on or after ≥1 prior line of systemic therapy in the metastatic setting.
  • Participants with locally advanced unresectable cervical cancer must have progressed on or after ≥1 prior lines 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, GEC, or CRC whose disease shows HER2 amplification/overexpression.
  • Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma 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, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial.


Banner University Medical Center - Tucson
Status: ACTIVE


Massachusetts General Hospital Cancer Center
Status: ACTIVE


Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE


Case Comprehensive Cancer Center
Status: ACTIVE


Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE


Fred Hutch / University of Washington Cancer Consortium
Status: ACTIVE


University of Wisconsin Hospital and Clinics
Status: ACTIVE

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, GEC, and CRC) or HER2-mutated solid tumor types.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Seagen Inc.

  • Primary ID SGNTUC-019
  • Secondary IDs NCI-2021-00125
  • ID NCT04579380