Enhertu (AstraZeneca and Daiichi Sankyo’s trastuzumab deruxtecan) has become the first tumor-agnostic, FDA-approved, HER2-directed therapy. It is approved for adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors. Enhertu is an antibody drug conjugate (ADC) that consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads via tetrapeptide-based cleavable linkers.
Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, said, “As the first antibody drug conjugate to be granted a tumor-agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2-targetable tumors. This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumors 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, president and CEO, Daiichi Sankyo, said, “This fifth indication in the U.S. is a significant milestone as eligible patients with previously treated metastatic HER2-positive solid tumors may now be treated with Enhertu.”
The FDA first approved Enhertu in December 2019 for HER2-positive unresectable or metastatic breast cancer in patients after two or more anti-HER2 therapies. The drug has since picked up other indications, including for gastric cancer and non-small cell lung cancer. Total sales of the drug were estimated to be $2.57 billion in 2023.
Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, U.S., said, “Until the approval of trastuzumab deruxtecan, patients with metastatic HER2-positive solid tumors have had limited treatment options. Based on the clinically meaningful response rates seen across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”
The drug gained accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval may be contingent upon a confirmatory trial. Its approval 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.
Enhertu’s safety was evaluated in 347 patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors in the DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. The safety profile observed across the trials was consistent with previous clinical trials of the drug with no new safety concerns identified.
