Enhertu Gets Accelerated Approval for HER2-Mutant Metastatic NSCLC

The accelerated approval was based on data from the phase 2 DESTINY-Lung02 trial that included adults with HER2-mutant metastatic NSCLC after 1 prior systemic therapy.

The Food and Drug Administration (FDA) has granted accelerated approval to Enhertu® (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.

The Life Technologies Corporation’s Oncomine Dx Target Test (tissue) and the Guardant Health, Inc.’s Guardant360® CDx (plasma) were also approved as companion diagnostics to detect activating HER2 mutations in patients with unresectable or metastatic NSCLC for treatment with Enhertu. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.

The accelerated approval was based on data from the multicenter, multicohort, randomized, blinded, phase 2 DESTINY-Lung02 trial (ClinicalTrials.gov Identifier: NCT04644237), which evaluated the efficacy and safety of Enhertu, a HER2 antibody-drug conjugate, in 52 adults with HER2-mutated metastatic NSCLC who had disease recurrence or progression after 1 prior systemic therapy. Patients received Enhertu 5.4mg/kg by intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.

Results showed a confirmed objective response rate of 57.7% (95% CI, 43.2-71.3); 1.9% of patients achieved complete response and 55.8% achieved partial response. The median duration of response was 8.7 months (95% CI, 7.1-not estimable). The safety profile of Enhertu was consistent with that observed in previous trials with no new safety concerns identified.

“HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “Today’s news provides these patients with the opportunity to benefit from a targeted therapy and highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease.”

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.


  1. Enhertu approved in the US as the first HER2-directed therapy for patients with previously treated HER2-mutant metastatic non-small cell lung cancer. News release. AstraZeneca and Daiichi Sankyo. Accessed August 12, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-approved-in-us-for-her2-mutant-nsclc.html
  2. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non-small cell lung cancer. News release. US Food and Drug Administration. Accessed August 12, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung
  3. Enhertu. Package insert. Daiichi Sankyo, Inc.; 2022. Accessed August 12, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761139s021lbl.pdf

This article originally appeared on MPR