Enhertu

HER2-positive unresectable or metastatic breast cancer after prior anti-HER2-based regimen; HER2-low unresectable or metastatic breast cancer after prior chemotherapy (or endocrine therapy if HR-positive); HER2-positive locally advanced or metastatic gastric/GEJ adenocarcinoma after prior trastuzumab-based regimen; Unresectable or metastatic HER2-mutant non-small cell lung cancer after prior systemic therapy

Breast cancer (HER2-positive): 5.4 mg/kg IV every 3 weeks
Breast cancer (HER2-low): 5.4 mg/kg IV every 3 weeks
Gastric cancer: 6.4 mg/kg IV every 3 weeks
NSCLC: 5.4 mg/kg IV every 3 weeks
Infusion time: 90 minutes for first infusion; may reduce to 30 minutes if tolerated

For injection: 100 mg lyophilized powder in single-dose vial for reconstitution

None listed.

• Interstitial Lung Disease/Pneumonitis: Fatal outcomes reported in 1.4% of patients. Median time to onset: 5.4 months.
• Neutropenia: Monitor CBCs prior to each dose.
• Left Ventricular Dysfunction: Monitor LVEF at baseline and during treatment.
• Embryo-Fetal Toxicity: Contains a genotoxic component (DXd). Verify pregnancy status before initiating.

Nausea (77%), fatigue (59%), vomiting (44%), alopecia (39%), constipation (36%), decreased appetite (35%), anemia (34%), neutropenia (33%), diarrhea (29%), thrombocytopenia (24%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Fam-trastuzumab deruxtecan is an antibody-drug conjugate composed of a humanized anti-HER2 IgG1 monoclonal antibody covalently linked to a topoisomerase I inhibitor payload (DXd, an exatecan derivative) via a cleavable tetrapeptide-based linker. It targets HER2-expressing cells, undergoes internalization, and releases DXd intracellularly to cause DNA damage and tumor cell death. The membrane-permeable DXd can also affect neighboring tumor cells (bystander effect).

Tmax: end of infusion. Half-life: ADC ~5.7 days; DXd (payload) ~5.8 days. Vd: 3.8 L. Clearance: 0.42 L/day. Steady-state by Cycle 3. DXd metabolized by CYP3A4. Minimal renal excretion.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• DESTINY-Breast03 — T-DXd vs. T-DM1 in HER2+ metastatic breast cancer after trastuzumab + taxane. Phase III, n=524.
  🔬 NCT03529110 ↗ 📄 Primary Publication ↗
• DESTINY-Breast04 — T-DXd vs. physician's choice in HER2-low metastatic breast cancer. Phase III, n=557.
  🔬 NCT03734029 ↗ 📄 Primary Publication ↗

Enhertu has FDA-approved indications across the following cancer types covered on PipelineEvidence: