FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors

Regulatory approval: On April 5, 2024, the FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu) for adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors after prior systemic therapy and with no satisfactory alternative options. The tumor-agnostic indication is based on objective response rate and duration of response from three multicenter trials; continued approval may depend on confirmatory evidence of clinical benefit.

FDA accelerated approval (Apr 5, 2024)

The FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo, Inc.) for adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.

Supporting evidence

Efficacy was evaluated in 192 previously treated adults enrolled across three multicenter trials: DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831). Major outcomes were confirmed ORR and DOR, assessed by independent central review per RECIST v1.1.

  • DESTINY-PanTumor02: ORR 51.4% (95% CI 41.7–61.0); median DOR 19.4 months (range 1.3–27.9+)
  • DESTINY-Lung01: ORR 52.9% (95% CI 27.8–77.0); median DOR 6.9 months (range 4.0–11.7+)
  • DESTINY-CRC02: ORR 46.9% (95% CI 34.3–59.8); DOR 5.5 months (range 1.3+–9.7+)

Trials excluded patients with prior steroid-treated ILD/pneumonitis or ILD/pneumonitis at screening, clinically significant cardiac disease, active brain metastases, or ECOG >1.

Safety and dosing

Most common adverse reactions (≥20%), including lab abnormalities, included cytopenias, nausea/vomiting, fatigue, transaminase/alkaline phosphatase increases, diarrhea/constipation, decreased appetite, alopecia, stomatitis, electrolyte decreases, and URTI. Labeling includes a Boxed Warning for interstitial lung disease and embryo-fetal toxicity. Recommended dose: 5.4 mg/kg IV every 3 weeks.

This tumor-agnostic indication was approved under accelerated approval; continued approval may be contingent on confirmatory trial(s). Review occurred under Project Orbis.

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