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

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.