AstraZeneca, Daiichi Sankyo Win First Tumor-Agnostic HER2 FDA Approval for Enhertu

Pictured: FDA's signage outside its office in Washington, DC

Pictured: FDA’s signage outside its office in Washington, DC

iStock, JHVEPhoto

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu is the first FDA-approved tumor-agnostic HER2-targeted therapy authorized for the treatment of solid tumors in adults who have undergone prior systemic treatment.

The FDA on Friday approved AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of HER2-positive solid tumors in adults who have undergone prior systemic treatment and have no alternative treatment options.

With Friday’s approval, Enhertu becomes the first tumor-agnostic HER2-directed therapy authorized for administration, and the first antibody-drug conjugate (ADC) to win such an indication, according to the companies.

The approval was granted under the FDA’s accelerated pathway using objective response rate (ORR) and duration of response (DoR) data. To keep Enhertu’s tumor-agnostic indication, AstraZeneca and Daiichi Sankyo will need to run a Phase III confirmatory trial to verify its clinical benefit.

Daiichi Sankyo CEO Ken Keller in a statement called the regulatory win a “significant milestone” for eligible patients across a broad range of tumor types, for whom Enhertu is now available as a treatment option.

“The accelerated approval by the FDA for this tumor-agnostic indication is based on the clinically meaningful efficacy seen with Enhertu across numerous types of metastatic cancers,” Keller added.

Data from the Phase II DESTINY-PanTumor02 trial, which enrolled nearly 470 patients with HER2-positve solid tumors, showed that Enhertu had an ORR of 37.1% after a median follow-up of 12.75 months, while its overall DOR was 11.3 months. The study recruited patients with a variety of tumor types, including biliary tract cancer, bladder cancer, cervical cancer, pancreatic cancer and certain rare tumors.

The results, which were published in October 2023 in the Journal of Clinical Oncology, demonstrated that the ADC also resulted in 6.9 months of median progression-free survival and 13.4 months of median overall survival.

Results from the DESTINY-Lung01 and DESTINY-CRC02 Phase II studies also supported Friday’s approval, which together showed that Enhertu has strong antitumor activity against metastatic non-small cell lung cancer and colorectal cancer.

Enhertu is an ADC that works by seeking out and binding to the HER2 protein, which is typically found on several solid tumors. Enhertu’s toxic payload is the small molecule DXd, a topoisomerase I inhibitor that is released inside the cancer cell and damages the DNA, triggering cell death.

The FDA first approved Enhertu in December 2019 for the treatment of HER2-positive unresectable or metastatic breast cancer in patients after two or more anti-HER2 therapies. Enhertu has since picked up several indications including for gastric cancer and non-small cell lung cancer.

The ADC carries a boxed warning for interstitial lung disease and embryo-fetal toxicity. Patients on Enhertu should be under tight monitoring for signs such as cough, dyspnea, fever and other respiratory symptoms.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at or

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at, or on LinkedIn.