AstraZeneca and Daiichi Sankyo’s ENHERTU (fam-trastuzumab deruxtecan-nxki), a specifically engineered HER2-directed antibody drug conjugate (ADC), has been approved by the U.S. FDA for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen and have developed disease recurrence during or within six months of completing therapy.
 
The approval was based on positive results from the DESTINY-Breast03 Phase III trial that showed ENHERTU reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (95% confidence interval) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
 
The approval was granted under the FDA’s Real-Time Oncology Review (RTOR) program and converts the accelerated approval of ENHERTU in later line HER2-positive metastatic breast cancer to standard approval, broadening ENHERTU’s breast cancer indication in the U.S. to earlier lines of use in patients with HER2-positive metastatic breast cancer. In the trial, the safety profile of ENHERTU was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.
 
Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (ENHERTU) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines®) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.
 
The U.S. regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration and Switzerland’s Swissmedic.
 
This approval follows the recent Priority Review and Breakthrough Therapy Designation of ENHERTU in the US in this earlier setting.
 
Regulatory applications for ENHERTU are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.