Phase 3 Study To Evaluate Fam-trastuzumab Deruxtecan-nxki in HER2+ Early Breast Cancer

November 3, 2020
Hannah Slater
Hannah Slater

The DESTINY-Breast05 trial will investigate fam-trastuzumab deruxtecan-nxki (Enhertu) versus ado-trastuzumab emtansine (T-DM1) as adjuvant therapy in patients with HER2-positive early breast cancer who have a high risk of disease recurrence and residual invasive disease in the breast or axillary lymph nodes after receiving neoadjuvant therapy.

Daiichi Sankyo and AstraZeneca announced the initiation of the global, head-to-head, phase 3 DESTINY-Breast05 trial, which will investigate fam-trastuzumab deruxtecan-nxki (Enhertu) versus ado-trastuzumab emtansine (T-DM1) as adjuvant therapy in patients with HER2-positive early breast cancer who have a high risk of disease recurrence and residual invasive disease in the breast or axillary lymph nodes after receiving neo-adjuvant therapy.

The trial will be conducted in collaboration with the National Surgical Adjuvant Breast and Bowel Project Foundation (NSABP), the German Breast Group (GBG), Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-B), and the SOLTI Breast Cancer Research Group.

“Despite recent improvements and approvals of new medicines, there remain significant clinical needs for patients with HER2-positive early breast cancer with residual invasive disease after completing neo-adjuvant treatment,” Antoine Yver, MD, MSc, executive vice president and global head of Oncology Research and Development at Daiichi Sankyo, said in a press release. “We recognize the important opportunity that exists post-surgery to slow disease progression with further adjuvant treatment.”

“This research builds on the data from DESTINY-Breast01 which showed durability of response in previously treated HER2 positive metastatic breast cancer,” Yver added. “DESTINY-Breast05 will evaluate [fam-trastuzumab deruxtecan-nxki] in patients with early HER2-positive breast cancer, versus T-DM1, the current standard of care, which marks the first time we will evaluate the clinical benefit of [fam-trastuzumab deruxtecan-nxki] in early breast cancer, reflecting our commitment to transforming treatment for even more patients with HER2 targetable disease.”

The multicenter, open-label, active-controlled DESTINY-Breast05 study of fam-trastuzumab deruxtecan-nxki versus T-DM1 will include patients defined as high-risk based on inoperable cancer at disease presentation (clinical stages T4, N0-3, M0 or T1-3, N2-3, M0) or operable at presentation (clinical stages T1-3, N0-1, M0) with positive pathological node status (ypN1-3) after neo-adjuvant therapy. The trial is planning to enroll up to 1600 patients at approximately 400 sites across North America, Europe, and Asia.

Patients will be randomized in 1:1 to receive either fam-trastuzumab deruxtecan-nxki or T-DM1. Randomization will be stratified by:

  • Operative status at disease presentation, prior to neo-adjuvant therapy (operable vs inoperable)
  • Tumor hormone receptor status (positive vs negative)
  • Post-neo-adjuvant therapy pathologic nodal status (positive vs negative)
  • HER2 targeted neo-adjuvant therapy approach (single vs dual)

The primary end point for the study is invasive disease-free survival based on investigator assessment. Key secondary end points include overall survival and disease-free survival based on disease recurrence per investigator assessment.

Moreover, safety end points include serious adverse events, treatment-emergent adverse events, and adverse events of special interest. Health economics and outcomes research endpoints as well as pharmacokinetic and biomarker endpoints will also be measured.

Reference:

DESTINY-Breast05 Head-to-Head Phase 3 Trial of ENHERTU® Versus T-DM1 Initiated in Patients with HER2 Positive Early Breast Cancer at High Risk After Neo-adjuvant Therapy [news release]. Tokyo, Munich, and Basking Ridge, NJ. Published November 2, 2020. Accessed November 2, 2020.