Accelerated Approval Granted to Trastuzumab Deruxtecan for HER2+ NSCLC

Adults with previously treated unresectable or metastatic non–small cell lung cancer whose tumors harbor HER2 mutations may now be treated with fam-trastuzumab deruxtecan-nxki.

Accelerated approval has been granted to fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) for the treatment of patients with HER2 mutation–positive unresectable or metastatic non–small cell lung cancer following prior systemic therapy, according to the FDA.1

In conjunction with this approval, the FDA also approved the Life Technologies Corporation’s OncomineDxTarget Test for tissue analysis and the Guardant360 CDx plasma assay as companion diagnostics.

“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. 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,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in the press release.2

The approval was based on results from the phase 2 DESTINY-Lung02 trial (NCT04644237) in which patients with unresectable or metastatic HER2-mutated nonsquamous NSCLC who had disease progression after prior systemic therapy were treated with T-DXd at 5.4 mg/kg intravenously every 3 weeks until unacceptable toxicity or disease progression.

In the dose-finding trial, T-DXd every 3 weeks was evaluated at 6.4 mg/kg in 152 patients and 5.4 mg/kg in 102 patients. Patients had consistent results but saw increased levels of interstitial lung disease or pneumonitis at the higher dose levels. The 5.4 mg/kg dosing level was determined to be the optimal dose.

Of the 52 patients in the primary efficacy population, the objective response rate (ORR) was 58% (95% CI, 43%-71%) and the duration of response was 8.7 months (95% CI, 7.1-not estimable). The most common adverse effects included laboratory abnormalities, nausea, decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, and decreased platelet count.

T-DXd was previously granted priority review based on results from the phase 2 DESTINY-Lung01 trial (NCT03505710) in 91 patients with HER2-mutated metastatic NSCLC cancer following treatment with prior systemic therapy.3

In this trial, patients had an ORR of 54.9% (95% CI, 44.2%-65.4%), with 53.8% of patients achieving a partial response and 1.1% achieving a complete response. Patients had a confirmed disease control rate of 92.3% and a median DOR of 9.3 months at the median follow-up of 13.1 months. The median progression-free survival was 8.2 months, and the median overall survival was 17.8 months.

“We are excited that the FDA has granted accelerated approval for Enhertu for patients with HER2-mutant metastatic non-small cell lung cancer. Enhertu has now been approved in three different tumor types, underscoring its significant potential across several HER2-targetable tumors. We are continuing to evaluate the efficacy and safety of Enhertu versus standard chemotherapy in our DESTINY clinical trials in lung cancer,” concluded Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc.


  1. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for HER2-mutant non–small cell lung cancer. News Release. FDA. August 11, 2022. Accessed August 12, 2022.
  2. 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. August 12, 2022. Accessed August 12, 2022.
  3. Enhertu granted priority review in the US for patients with previously treated HER2-mutant metastatic non-small cell lung cancer. News release. AstraZeneca and Daiichi Sankyo. April 19, 2022. Accessed August 12, 2022.