FDA Grants Accelerated Approval to Trastuzumab Deruxtecan for Unresectable or Metastatic HER2-Positive Solid Tumors

On April 5, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to trastuzumab deruxtecan for patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive solid tumors who received systemic treatment and have no alternative treatment options. 

This regulatory decision was based on results from the DESTINY-PanTumor02, DESTINY-LUNG01, and DESTINY-CRC02 trials. Across all 3 trials, 192 patients with previously treated unresectable or metastatic HER2-positive solid tumors were enrolled to receive 5.4 mg/kg of trastuzumab deruxtecan once every 3 weeks in a 21-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Patients were excluded from trial enrollment if they had a history of interstitial lung disease/pneumonitis requiring treatment with steroids or interstitial lung disease/pneumonitis at screening and clinically significant cardiac disease. Additionally, patients with active brain metastases or an ECOG performance status >1 were excluded. The main efficacy outcomes included confirmed objective response rate (ORR) and median duration of response (DOR), assessed by independent central review. 

At analysis, ORR in DESTINY-PanTumor02 was 51.4% (95% confidence interval [CI], 41.7 to 61) with a median DOR of 19.4 months. In DESTINY-LUNG01, ORR was 52.9% (95% CI, 27.8 to 77) with a median DOR of 6.9 months. In DESTINY-CRC02, ORR was 46.9% (95% CI, 34.3 to 59.8) with a median DOR of 5.5 months. The most common adverse reactions occurring in ≥20% patients, including laboratory abnormalities, included decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, fatigue, decreased lymphocyte count, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, decreased appetite, alopecia, diarrhea, decreased blood potassium, constipation, decreased sodium, stomatitis, and upper respiratory tract infection. 

There is a boxed warning for risk of interstitial lung disease and embryo-fetal toxicity. The recommended dose of trastuzumab deruxtecan is 5.4 mg/kg once every 3 weeks in a 21-day cycle until disease progression or unacceptable toxicity.

Source: 

FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. Published online: April 5, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-unresectable-or-metastatic-her2