FDA D.I.S.C.O. Burst Edition: FDA approval of Enhertu (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 solid tumors who have received prior systemic therapy and have no satisfactory alternative treatment options. The decision was supported by objective response rate and duration of response results from three multicenter trials (DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02). Labeling includes a Boxed Warning for interstitial lung disease and embryo-fetal toxicity.

FDA accelerated approval (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 solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.

Supporting evidence

Efficacy was evaluated in 192 adults with previously treated unresectable or metastatic HER2-positive solid tumors enrolled across three multicenter trials: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. Across all three studies, major efficacy outcome was confirmed objective response rate (ORR), with duration of response (DOR) as an additional outcome; assessments were by independent central review per RECIST v1.1.

  • DESTINY-PanTumor02: ORR 51.4%; median DOR 19.4 months
  • DESTINY-Lung01: ORR 52.9%; median DOR 6.9 months
  • DESTINY-CRC02: ORR 46.9%; DOR 5.5 months

Key exclusions in all three trials included prior or current interstitial lung disease/pneumonitis (steroid-requiring history or present at screening), clinically significant cardiac disease, active brain metastases, or ECOG >1.

Safety and regulatory context

Prescribing information includes a Boxed Warning for interstitial lung disease and embryo-fetal toxicity. The review was conducted under Project Orbis; reviews at other agencies were ongoing at the time of the update.

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