The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for fam-trastuzumab deruxtecan-nxki (Enhertu®) for the treatment of adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy.

The sBLA is supported by data from the registrational, multicenter, open-label, 2-cohort phase 2 DESTINY-Lung01 trial ( Identifier: NCT03505710) evaluating the efficacy and safety of fam-trastuzumab deruxtecan-nxki, a HER2 antibody-drug conjugate, in adults with HER2-overexpressing and/or HER2-mutated advanced NSCLC. The trial enrolled 91 adults with metastatic HER2-mutant NSCLC that were refractory to standard treatment (cohort 2), who received fam-trastuzumab deruxtecan-nxki 6.4mg/kg intravenously. 

The primary endpoint was overall response rate (ORR) as assessed by independent central review based on RECIST v1.1. Secondary endpoints included the duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

After a median duration of follow-up of 13.1 months for cohort 2, results showed a confirmed ORR of 54.9% (95% CI, 44.2-65.4), of which 1 (1.1%) patient achieved complete response and 49 (53.8%) patients achieved partial responses. The median DoR was 9.3 months (95% CI, 5.7-14.7). The median PFS was 8.2 months (95% CI, 6-11.9) and the median OS was 17.8 months (95% CI, 13.8-22.1). Moreover, a confirmed disease control rate of 92.3% was observed with a reduction in tumor size seen in most patients. 

The safety profile for fam-trastuzumab deruxtecan-nxki was consistent with its known profile in previous studies. There were no new safety concerns identified. Additionally, the sBLA is supported by data from a phase 1 trial ( Identifier: NCT02564900) published in Cancer Discovery.

A Prescription Drug User Fee Act (PDUFA) target date during the third quarter of 2022 is set for this application.

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said, “The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable biomarker in non-small cell lung cancer. If approved, Enhertu has the potential to become a new standard treatment in this patient population, offering a much-needed option for patients with HER2-mutant metastatic non-small cell lung cancer who currently have no targeted treatment options.”

The FDA previously granted Breakthrough Therapy designation to fam-trastuzumab deruxtecan-nxki for this indication.


  1. Enhertu® (fam-trastuzumab deruxtecan-nxki) 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. Accessed April 19, 2022.
  2. Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non–small-cell lung cancer. N Engl J Med. Published online January 20, 2022. doi: 10.1056/NEJMoa2112431