On December 20, 2019, the Food and Drug Administration granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu®) for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.
Efficacy was investigated in DESTINY-Breast01 (NCT03248492), a multicenter, single-arm trial enrolling 184 women with HER2-positive, unresectable or metastatic breast cancer who had received two or more prior anti-HER2 therapies. Patients received fam-trastuzumab deruxtecan-nxki 5.4 mg/kg by IV infusion every three weeks until unacceptable toxicity or disease progression.
The main efficacy outcome measures were confirmed objective response rate (ORR) assessed by independent central review using RECIST 1.1 and response duration. ORR was 60.3% (95% CI: 52.9, 67.4), with a 4.3% complete response rate and a 56% partial response rate. Median response duration was 14.8 months (95% CI = 13.8, 16.9).
The safety was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of fam-trastuzumab deruxtecan-nxki 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101 (NCT02564900). The most common adverse reactions (≥ 20%) to fam-trastuzumab deruxtecan-nxki were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia. The prescribing information includes a boxed warning to advise health professionals of the risk of interstitial lung disease (ILD) and embryo-fetal toxicity. Fatal outcomes from ILD occurred in 2.6% of patients.
The recommended fam-trastuzumab deruxtecan-nxki dose is 5.4 mg/kg given as an IV infusion once every three weeks (21-day cycle) until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA granted this application breakthrough therapy designation. Fam-trastuzumab deruxtecan-nxki also was granted fast-track designation and priority review. The application was approved four months ahead of the FDA goal date.
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For assistance with single-patient new drug applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.