Trastuzumab deruxtecan

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer as neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP). as adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment.

Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.

Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. For intravenous infusion only. Do not administer as an intravenous push or bolus. DO NOT use Sodium Chloride Injection, USP. Premedicate for prevention of chemotherapy-induced nausea and vomiting. HER2-Positive Early Breast Cancer Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 4 cycles, followed by THP regimen for 4 cycles. Post Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 14 cycles unless disease recurrence or unacceptable toxicity. HER2-Positive, HER2-Low, or HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (IHC 3+) Solid Tumors: ENHERTU 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. HER2-Positive First-line Metastatic Breast Cancer: ENHERTU 5.4 mg/kg every 3 weeks in combination with pertuzumab until disease progression or unacceptable toxicity.

None. None.

Boxed warning (interstitial lung disease and embryo-fetal toxicity): Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Neutropenia: Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Manage through treatment interruption or dose reduction. Left Ventricular Dysfunction (LVD): Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage through treatment interruption or discontinuation.

The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis Neutropenia Left Ventricular Dysfunction The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with: HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (including IHC 3+) Solid Tumors are decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, fatigue, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, alopecia, constipation, decreased blood potassium, decreased appetite, diarrhea, and musculoskeletal pain.

Do not freeze. Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not shake the reconstituted or diluted solution.