AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved by the U.S. FDA for the treatment of adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.
 
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
 
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
 
The first tumor-agnostic approval of a HER2-directed therapy and ADC by the FDA was based on results from the subgroup of patients with HER2-positive IHC 3+ tumors in each of the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 Phase II trials.
 
In the DESTINY-PanTumor02 Phase II trial, patients with centrally or locally assessed HER2-positive (IHC 3+) solid tumors including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumors treated with Enhertu showed a confirmed ORR of 51.4% and a median DoR range of 19.4 months. In DESTINY-Lung01, patients with centrally confirmed HER2-positive (IHC 3+) non-small cell lung cancer (NSCLC) treated with Enhertu showed a confirmed ORR of 52.9% and median DoR range of 6.9 months. A confirmed ORR of 46.9%  and median DoR range of 5.5 months was seen in patients with centrally confirmed HER2-positive (IHC 3+) colorectal cancer in the DESTINY-CRC02 trial.