FDA grants approval to fam-trastuzumab deruxtecan-nxki (ENHERTU®)

From the American Society of Clinical Oncology in cooperation with the Food and Drug Administration (FDA) and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields about recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On December 20, 2019, the Food and Drug Administration granted accelerated approval to fam-trastuzumab deruxtecan-nxki (ENHERTU®, Daiichi Sankyo) 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 female patients with HER2-positive, unresectable and/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 intravenous infusion every 3 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 (frequency ≥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 due to ILD occurred in 2.6% of patients.

The recommended fam-trastuzumab deruxtecan-nxki dose is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

View full prescribing information for ENHERTU.

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. This application was approved 4 months ahead of the FDA goal date.

A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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