FDA Grants Accelerated Approval to Trastuzumab Deruxtecan for HER2+ Metastatic NSCLC

Accelerated approval has been granted to trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic non-small cell lung cancer based on positive results from DESTINY-Lung02.

The FDA has granted accelerated approval to trastuzumab deruxtecan for the treatment of patients unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.1

Accelerated approval was granted based on the objective response rate (ORR), and duration of response (DOR) observed with trastuzumab deruxtecan in the phase 2 DESTINY-Lung02 trial (NCT04644237).

“The approval of trastuzumab deruxtecan in non-small cell lung cancer is an important milestone for patients and the oncology community. After two decades of research into the role of targeting HER2 in lung cancer, the approval of the first HER2-directed treatment option validates HER2 as an actionable target in lung cancer and marks an important step forward for treating this patient population with unmet medical needs, said Bob T. Li, MD, PhD, MPH, medical oncologist and physician-scientist at Memorial Sloan Kettering Cancer Center, in a press release.

In 152 patients treated with trastuzumab deruxtecan 5.4mg/kg or 6.4mg/kg, the ORR 57.7% (95% CI, 43.2-71.3) in patients with previously treated unresectable or metastatic non-squamous HER2-mutant (HER2m) NSCLC, as assessed by blinded independent central review (BICR). The complete response rate observed with trastuzumab deruxtecan was 1.9%, and the partial response rate was 55.8. the median DOR 8.7 months (95% CI 7.1-NE). According to AstraZeneca, full results from DESTINY-Lung02 trial will be presented at an upcoming medical meeting.

The multicenter, randomized study continues to evaluate ORR by BICR as well as secondary end point including, ORR by investigator assessment, DOR, disease control rate, progression-free survival, overall survival, the percentage of patients with treatment-emergent adverse events, pharmacokinetics, the number of patients with anti-drug antibodies, and quality of life.

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

Trastuzumab deruxtecan is now the first HER2-directed therapy approved for the treatment of patients with previously treated HER2-mutant metastatic NSCLC. In addition to the accelertated FDA approval of the drug, the FDA granted approval to the Oncomine Dx Target Test and the Guardant360 CDx as companion diagnostics to detect HER2 mutations in patients with metastatic NSCLC.


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.

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