FDA Approves Fam-Trastuzumab Deruxtecan-nxki for HER2-positive Gastric Adenocarcinomas

January 19, 2021

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On January 15, 2021, the Food and Drug Administration approved fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo) for adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

Efficacy was evaluated in a multicenter, open-label, randomized trial (DESTINY-Gastric01, NCT03329690) in patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens, including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy. A total of 126 patients were randomized (2:1) to receive fam-trastuzumab deruxtecan-nxki 6.4 mg/kg intravenously every 3 weeks or physician’s choice of either irinotecan or paclitaxel monotherapy.

The main efficacy outcome measures were overall survival (OS) and objective response rate (ORR) assessed by independent central review (RECIST 1.1) in the intent-to-treat population. Additional efficacy outcome measures were progression-free survival (PFS) and duration of response (DOR).

OS was 12.5 months (95% CI: 9.6, 14.3) in the fam-trastuzumab deruxtecan-nxki arm compared with 8.4 months (95% CI: 6.9, 10.7) in the irinotecan or paclitaxel arm (HR 0.59; 95% CI: 0.39, 0.88, p=0.0097). Confirmed ORR was 40.5% (95% CI: 31.8, 49.6) in the fam-trastuzumab deruxtecan-nxki arm compared with 11.3% (95% CI: 4.7, 21.9) for those receiving irinotecan or paclitaxel. Median PFS was 5.6 months (95% CI: 4.3, 6.9) in the fam-trastuzumab deruxtecan-nxki arm compared to median PFS of 3.5 months (95% CI: 2.0, 4.3) in the irinotecan or paclitaxel arm. Median DOR was 11.3 months (95% CI: 5.6, NR) vs 3.9 months (95% CI: 3.0, 4.9), respectively.

The most common (≥ 20%) adverse reactions including laboratory abnormalities were anemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, hypokalemia, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia. The Prescribing Information includes a Boxed Warning to advise health professionals of the risks of interstitial lung disease and embryo-fetal toxicity.

The recommended fam-trastuzumab deruxtecan-nxki dose for gastric cancer is 6.4 mg/kg administered 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 the FDA’s assessment. The FDA approved this application approximately 6 weeks ahead of the FDA goal date.

This application was granted priority review. Fam-trastuzumab deruxtecan-nxki was granted breakthrough therapy designation and orphan drug designation in gastric cancer. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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