Ian Krop, MD, Ph.D., Associate Cancer Center Director for Clinical Research; Yale Cancer Center. In this video, he speaks about the ASCO 2022 abstract - 486a – Phase 2 Trial of Tucatinib plus Trastuzumab Deruxetan in Patients with HER2+ Locally Advanced or Metastatic Breast Cancer with and without Brain Metastases (HER2CLIMB-04, trial in progress).
Tucatinib is a reversible small-molecule tyrosine kinase inhibitor administered orally that is highly selective for human epidermal growth factor receptor 2. (HER2). Tucatinib is licensed in the United States for treatment in adult patients with HER2+ metastatic breast cancer (MBC), with or without brain metastases, who have received at least one prior anti–HER2-based therapy in the metastatic context. T-DXd, an antibody–drug conjugate (ADC) containing a HER2-directed monoclonal antibody conjugated to a topoisomerase I inhibitor payload, is also approved in the United States for patients with HER2+ MBC. Tucatinib improved the anticancer activity of a HER2-directed ADC comprised of a HER2-directed monoclonal antibody conjugated with 8 exatecan moieties (T-Ex) in HER2+ breast cancer (BC) xenograft animals when compared to T-Ex alone (Kulukian et al 2019). Despite substantial progress in the treatment of individuals with HER2+ breast cancer, treating metastatic illness remains a clinical challenge due to limited therapy options.
HER2CLIMB-04 (NCT04539938) is a multicenter, single-arm, open-label phase 2 research investigating the efficacy and safety of tucatinib plus T-DXd in previously treated patients aged 18 years with unresectable, locally advanced, or metastatic (LA/M) HER2+ breast cancer. Patients must have received prior treatment in the LA/M context with a taxane and trastuzumab (with or without pertuzumab) or progressed within 6 months of neoadjuvant or adjuvant treatment utilizing a taxane and trastuzumab regimen (with or without pertuzumab). Patients with brain metastases, particularly active brain metastases, may be eligible to participate. The study's safety lead-in phase, which included 10 patients who were followed for at least one cycle, has been completed. Because this portion of the study indicated a tolerable safety profile, the trial will enroll roughly 60 response-evaluable patients (including the 10 from the safety lead-in), evenly split between patients with and without brain metastases. The primary outcome is the confirmed objective response rate (cORR) as determined by investigator assessment in accordance with RECIST 1.1. Secondary objectives include progression-free survival (PFS), duration of response (DOR), disease control rate (DCR) according to RECIST 1.1, overall survival, and safety. cORR, PFS, DCR, and DOR by independent central review per RECIST 1.1, pharmacokinetic analysis, biomarker analyses, and changes in patient-reported outcomes will be exploratory objectives. Descriptive statistics will be used to summarize efficacy and safety. Enrollment in the United States commenced in late 2020. NCT04539938 is the clinical trial number.