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Fam-Trastuzumab Deruxtecan-Nxki

FDA Drug Information • Also known as: Enhertu

Brand Names
Enhertu
Route
INTRAVENOUS
Dosage Form
INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including 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. Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . Embryo-Fetal Toxicity: Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ] . WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Interstitial lung disease (ILD) and pneumonitis, including 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. Advise patients of the risk and to immediately report symptoms. ( 2.3 , 5.1 ) Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. ( 5.4 , 8.1 , 8.3 )

Description

11 DESCRIPTION Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate. Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate (ADC) composed of three components: 1) a humanized anti-HER2 IgG1 monoclonal antibody (mAb), covalently linked to 2) a topoisomerase inhibitor, via 3) a tetrapeptide-based cleavable linker. Deruxtecan is composed of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd, which is an exatecan derivative. The antibody is produced in Chinese hamster ovary cells by recombinant DNA technology, and the topoisomerase inhibitor and linker are produced by chemical synthesis. Approximately 8 molecules of deruxtecan are attached to each antibody molecule. Fam-trastuzumab deruxtecan-nxki has the following structure: ENHERTU (fam-trastuzumab deruxtecan-nxki) is a sterile, white to yellowish white, preservative-free lyophilized powder in single-dose vials. Each vial delivers 100 mg of fam-trastuzumab deruxtecan-nxki, L-histidine (4.45 mg), L-histidine hydrochloride monohydrate (20.2 mg), polysorbate 80 (1.5 mg), and sucrose (450 mg). Following reconstitution with 5 mL of Sterile Water for Injection, USP, the resulting concentration of fam-trastuzumab deruxtecan-nxki is 20 mg/mL with a pH of 5.5. The resulting solution is administered by intravenous infusion following dilution. Chemical Structure

What Is Fam-Trastuzumab Deruxtecan-Nxki Used For?

1 INDICATIONS AND USAGE ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated: HER2-Positive Metastatic Breast Cancer in combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test. ( 1.1 ) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. ( 1.1 ) HER2-Low and HER2-Ultralow Metastatic Breast Cancer as monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting. ( 1.2 ) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting; or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. ( 1.2 ) HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer as monotherapy for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy* ( 1.3 ) HER2-Positive Locally Advanced or Metastatic Gastric Cancer as monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. ( 1.4 ) HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options* ( 1.5 ) * These indications are approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ( 14.3 , 14.5 ) 1.1 HER2-Positive Metastatic Breast Cancer ENHERTU, in combination with pertuzumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-approved test [see Dosage and Administration (2.1) ]. ENHERTU, as monotherapy, is indicated for the treatment of adult patients...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. ( 2.2 , 2.4 ) For intravenous infusion only . Do not administer as an intravenous push or bolus. DO NOT use Sodium Chloride Injection, USP. ( 2.4 ) Premedicate for prevention of chemotherapy-induced nausea and vomiting. ( 2.2 ) 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. ( 2.2 , 2.3 ) 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. Cycle 1, Day 1: ENHERTU 5.4 mg/kg followed by pertuzumab 840 mg. ( 2.2 , 2.3 ) Subsequent cycles, Day 1: ENHERTU 5.4 mg/kg followed by pertuzumab 420 mg. ( 2.2 , 2.3 ) HER2-positive gastric cancer: 6.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. ( 2.2 , 2.3 ) Management of adverse reactions (ILD, neutropenia, thrombocytopenia, or left ventricular dysfunction) may require temporary interruption, dose reduction, or discontinuation of ENHERTU. ( 2.3 ) 2.1 Patient Selection HER2-Positive Metastatic Breast Cancer Select patients for treatment of unresectable or metastatic HER2-positive breast cancer with ENHERTU in combination with pertuzumab based on confirmed HER2-positive status or HER2 gene amplification (IHC 3+ or ISH+) [see Clinical Studies (14.1) ] . HER2-Low or HER2-Ultralow Unresectable or Metastatic Breast Cancer Select patients for treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer with ENHERTU based on HER2 expression [see Clinical Studies (14.2) ] . HER2-Mutant Unresectable or Metastatic NSCLC Select patients for the treatment of unresectable or metastatic HER2-mutant NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations in tumor or plasma specimens [see Clinical Studies (14.3) ] . If no mutation is detected in a plasma specimen, test tumor tissue. HER2-Positive Locally Advanced or Metastatic Gastric Cancer Select patients with locally advanced or metastatic HER2-positive gastric cancer based on HER2 protein overexpression or HER2 gene amplification (IHC 3+ or IHC 2+/ISH+). Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU. HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors Select patients for treatment of unresectable or metastatic solid tumors with ENHERTU based on HER2-positive (IHC 3+) specimens [see Clinical Studies (14.5) ] . An FDA-approved test for the detection of HER2-positive (IHC 3+) solid tumors for treatment with ENHERTU is not currently available. Additional Patient Selection Information Information on FDA-approved tests for the detection of HER2 protein expression, HER2 gene...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with: HER2-positive, HER2-low, and HER2-ultralow metastatic 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. ( 6.1 ) HER2-positive metastatic breast cancer in treatment with ENHERTU in combination with pertuzumab are decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, nausea, increased alanine aminotransferase, diarrhea, increased aspartate aminotransferase, decreased lymphocyte count, decreased platelet count, increased blood alkaline phosphatase, decreased blood potassium, fatigue, alopecia, vomiting, upper respiratory tract infection, constipation, decreased appetite, decreased weight, COVID-19, musculoskeletal pain, increased blood bilirubin, and abdominal pain. ( 6.1 ) HER2-positive gastric cancer are decreased hemoglobin, decreased white blood cell count, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, decreased blood potassium, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) The pooled safety population described in WARNINGS and PRECAUTIONS reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY- Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for greater than 6 months and 38% were exposed for greater than 12 months. In this pooled safety population, the most common (≥20%) adverse reactions (including laboratory abnormalities) were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%). ENHERTU in Combination with Pertuzumab The pooled safety population described in WARNINGS and PRECAUTIONS reflects exposure to ENHERTU 5.4 mg/kg in combination with pertuzumab intravenously every 3 weeks in 431 patients in DESTINY-Breast07 (n=50), and DESTINY-Breast09 (n=381). Among these patients, 86% were exposed for greater than 6 months and 73% were exposed for greater than 12...

Contraindications

4 CONTRAINDICATIONS None . None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action, ENHERTU can cause fetal harm when administered to a pregnant woman. There are no available data on the use of ENHERTU in pregnant women. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death ( see Data ). Based on its mechanism of action, the topoisomerase inhibitor component of ENHERTU, DXd, can also cause embryo-fetal harm when administered to a pregnant woman because it is genotoxic and targets actively dividing cells [see Clinical Pharmacology (12.1) , Nonclinical Toxicology (13.1) ] . Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU ( see Clinical Considerations ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received ENHERTU during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data There are no available data on the use of ENHERTU in pregnant women. In postmarketing reports in pregnant women receiving a HER2-directed antibody, cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported. These case reports described oligohydramnios in pregnant women who received a...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied/Storage ENHERTU (fam-trastuzumab deruxtecan-nxki) for injection is a white to yellowish white lyophilized powder supplied as: Carton Contents NDC One 100 mg single-dose vial NDC 65597-406-01 Store vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution [see Dosage and Administration (2.4) ] . Special Handling ENHERTU (fam-trastuzumab deruxtecan-nxki) is a hazardous drug. Follow applicable special handling and disposal procedures. 1

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.