Enhertu

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 amplification, and activating HER2 mutations is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Schedules Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. Slow or interrupt the infusion rate if the patient develops infusion-related symptoms. Permanently discontinue ENHERTU in case of severe infusion reactions. Premedication ENHERTU is highly emetogenic [see Adverse Reactions (6.1) ] , which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications per local institutional guidelines for prevention of chemotherapy-induced nausea and vomiting. The recommended dosages for ENHERTU as monotherapy and ENHERTU in combination with pertuzumab are presented in Table 1. Administer ENHERTU as an intravenous infusion [see Dosage and Administration (2.4) ]. Table 1: Recommended Dosage Indication Recommended ENHERTU Dosage Duration of Therapy HER2-Positive, HER2-Low, or HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant Unresectable or Metastatic NSCLC, and HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors as monotherapy ENHERTU 5.4 mg/kg every 3 weeks Until disease progression or unacceptable toxicity HER2-Positive Metastatic Breast Cancer in combination with pertuzumab Cycle 1, Day 1: ENHERTU 5.4 mg/kg, followed by pertuzumab 840 mg Administer pertuzumab 30 minutes after ENHERTU. Subsequent cycles, Day 1: ENHERTU 5.4 mg/kg, followed by pertuzumab 420 mg every 3 weeks Until disease progression or unacceptable toxicity HER2-Positive Locally Advanced or Metastatic Gastric Cancer as monotherapy ENHERTU 6.4 mg/kg every 3 weeks Until disease progression or unacceptable toxicity 2.3 Dosage Modifications Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of ENHERTU as described in Tables 2 and 3. Refer to the Prescribing Information for pertuzumab for dose modification recommendations. Pertuzumab is not to be administered as a single agent. Do not re-escalate the ENHERTU dose after a dose reduction is made . If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion. Table 2: Dosage Reduction Schedule Dose Reduction Schedule Breast Cancer, NSCLC, and IHC 3+ Solid Tumors Gastric Cancer Recommended starting dose 5.4 mg/kg 6.4 mg/kg First dose reduction 4.4 mg/kg 5.4 mg/kg Second dose reduction 3.2 mg/kg 4.4 mg/kg Requirement for further dose reduction Discontinue treatment. Discontinue treatment. Table 3: Dosage Modifications for Adverse Reactions Adverse Reaction Severity Treatment Modification Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v.5.0). Interstitial Lung Disease (ILD)/ Pneumonitis [see Warnings and Precautions (5.1) ] Asymptomatic ILD/pneumonitis (Grade 1) Interrupt ENHERTU until resolved to Grade 0, then: if resolved in 28 days or less from date of onset, maintain dose. if resolved in greater than 28 days from date of onset, reduce dose one level (see Table 1 ). consider corticosteroid treatment as soon as ILD/pneumonitis is suspected. Symptomatic ILD/pneumonitis (Grade 2 or greater) Permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected. Neutropenia [see Warnings and Precautions (5.2) ] Grade 3 (less than 1.0 to 0.5 × 10 9 /L) Interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. Grade 4 (less than 0.5 × 10 9 /L) Interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level (see Table 1 ). Febrile Neutropenia [see Warnings and Precautions (5.2) ] Absolute neutrophil count of less than 1.0 × 10 9 /L and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour Interrupt ENHERTU until resolved. Reduce dose by one level (see Table 1 ). Thrombocytopenia [see Adverse Reactions (6.1) ] Grade 3 (platelets less than 50 to 25 × 10 9 /L) Interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. Grade 4 (platelets less than 25 × 10 9 /L) Interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level (see Table 1 ). Left Ventricular Dysfunction [see Warnings and Precautions (5.3) ] LVEF greater than 45% and absolute decrease from baseline is 10% to 20% Continue treatment with ENHERTU. LVEF 40% to 45% And absolute decrease from baseline is less than 10% Continue treatment with ENHERTU. Repeat LVEF assessment within 3 weeks. And absolute decrease from baseline is 10% to 20% Interrupt ENHERTU. Repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. LVEF less than 40% or absolute decrease from baseline is greater than 20% Interrupt ENHERTU. Repeat LVEF assessment within 3 weeks. If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue ENHERTU. Symptomatic congestive heart failure (CHF) Permanently discontinue ENHERTU. 2.4 Preparation and Administration In order to prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is ENHERTU (fam-trastuzumab deruxtecan-nxki) and not trastuzumab or ado-trastuzumab emtansine. Reconstitute and further dilute ENHERTU prior to intravenous infusion. Use appropriate aseptic technique. ENHERTU (fam-trastuzumab deruxtecan-nxki) is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Reconstitution Reconstitute immediately before dilution. More than one vial may be needed for a full dose. Calculate the dose (mg), the total volume of reconstituted ENHERTU solution required, and the number of vial(s) of ENHERTU needed [see Dosage and Administration (2.2) ] . Reconstitute each 100 mg vial by using a sterile syringe to slowly inject 5 mL of Sterile Water for Injection, USP into each vial to obtain a final concentration of 20 mg/mL. Swirl the vial gently until completely dissolved. Do not shake . If not used immediately, store the reconstituted ENHERTU vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours from the time of reconstitution, protect the vial from light. Do not freeze . The product does not contain a preservative. Discard unused ENHERTU after 24 hours refrigerated. Dilution Withdraw the calculated amount from the vial(s) using a sterile syringe. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear and colorless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discolored. Dilute the calculated volume of reconstituted ENHERTU in an intravenous infusion bag containing 100 mL of 5% Dextrose Injection, USP . DO NOT use Sodium Chloride Injection, USP. ENHERTU is compatible with an infusion bag made of polyvinylchloride or polyolefin (copolymer of ethylene and polypropylene). Gently invert the infusion bag to thoroughly mix the solution. Do not shake . Cover the infusion bag to protect from light. Discard any unused portion left in the vials. Administration If not used immediately, store the diluted ENHERTU in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours or at room temperature between 20ºC to 25ºC (68ºF to 77 ºF) for up to 4 hours including preparation and infusion time. Protect from light. Do not freeze . The maximum time from reconstitution of the vial through the end of administration should not exceed 24 hours. If the prepared infusion solution was stored refrigerated (2ºC to 8ºC [36ºF to 46ºF]), allow the solution to reach room temperature prior to administration. Cover the infusion bag to protect from light. Administer ENHERTU as an intravenous infusion only with an infusion set made of polyolefin or polybutadiene. Administer ENHERTU with a 0.20 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter. Do NOT administer as an intravenous push or bolus. Cover the infusion bag to protect from light during administration. Do not mix ENHERTU with other drugs or administer other drugs through the same intravenous line. First infusion: Administer infusion over 90 minutes. Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated.

See official label

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.