AstraZeneca (AZ) and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been granted accelerated approval by the US Food and Drug Administration (FDA) to treat a subset of patients with advanced solid tumours.
The HER2-directed antibody drug conjugate (ADC) has specifically been approved to treat adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options.
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of various tissue cells throughout the body. However, in some cancers, HER2 expression is amplified or the cells have activating mutations, and HER2 protein overexpression is often associated with aggressive disease and poor prognosis.
The FDA’s decision was supported by positive results from the subgroup of patients with HER2-positive (IHC 3+) tumours in each of the mid-stage DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials.
In DESTINY-PanTumor02, patients with centrally or locally assessed HER2-positive (IHC 3+) solid tumours, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic and other tumours, who were treated with Enhertu showed a confirmed objective response rate (ORR) of 51.4% and a median duration of response (DoR) range of 19.4 months.
In DESTINY-Lung01, Enhertu-treated patients with centrally confirmed HER2-positive (IHC 3+) non-small cell lung cancer showed a confirmed ORR of 52.9% and a median DoR range of 6.9 months, while those in DESTINY-CRC02 with centrally confirmed HER2-positive (IHC 3+) colorectal cancer had aconfirmed ORR of 46.9% and a median DoR range of 5.5 months.
Dave Fredrickson, executive vice president, oncology business unit, AZ, said: “As the first ADC to be granted a tumour-agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2-targetable tumours.”
Fredrickson added that the approval “elevates” the importance of testing for biomarkers, including HER2, across a broad range of tumours to “ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them”.
Ken Keller, global head of oncology business, and president and chief executive officer, Daiichi Sankyo, added: “This fifth indication in the US is a significant milestone as eligible patients with previously treated metastatic HER2-positive solid tumours may now be treated with Enhertu.”