Elahere

2.1 Patient Selection

Select patients for the treatment of platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with ELAHERE based on the presence of FRα tumor expression [see Indications & Usage ( 1) and Clinical Studies ( 14)] using an FDA-approved test.

Information on FDA-approved tests for the measurement of FRα tumor expression is available at http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage

The recommended dosage of ELAHERE is 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity [see Dosage and Administration ( 2.5)]. Dosing based on AIBW reduces exposure variability for patients who are either under or overweight.

The total dose of ELAHERE is calculated based on each patient’s AIBW using the following formula:

        AIBW = Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg] – IBW)

        Female IBW [kg] = 0.9*height[cm] – 92

2.3 Premedication and Required Eye Care

Premedication 

Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting. 

Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs. 

Ophthalmic Exams and Premedication

Ophthalmic Exam: Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

Ophthalmic Topical Steroids: The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE [see Warnings and Precautions ( 5.1)].

Lubricating Eye Drops: The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops [see Warnings and Precautions ( 5.1)].

2.4 Dosage Modifications

Table 2 provides dose reduction levels and Table 3 provides dosage modifications for ELAHERE due to adverse reactions.

* Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.

* Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

2.5 Instructions for Preparation and Administration

Preparation

• ELAHERE is a hazardous drug. Follow applicable special handling and disposal procedures1.
  
• Calculate the dose (mg) (based on the patient’s AIBW), total volume (mL) of solution required, and the number of vials of ELAHERE needed [see Recommended Dosage ( 2.2) and Dose Modifications ( 2.4)]. More than one vial will be needed for a full dose.
  
• Remove the vials of ELAHERE from the refrigerator and allow to warm to room temperature.
  
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ELAHERE is a clear to slightly opalescent, colorless solution.
  
• Gently swirl and inspect each vial prior to withdrawing the calculated dose volume of ELAHERE. Do not shake the vial.
  
• Using aseptic technique, withdraw the calculated dose volume of ELAHERE for subsequent dilution.
  
• ELAHERE contains no preservatives and is intended for single-dose only. Discard any unused drug remaining in the vial.

Dilution

• ELAHERE must be diluted prior to administration with 5% Dextrose Injection, USP to a final concentration of 1 mg/mL to 2 mg/mL.
  
• ELAHERE is incompatible with 0.9% Sodium Chloride Injection. ELAHERE must not be mixed with any other drugs or intravenous fluids.
  
• Determine the volume of 5% Dextrose Injection, USP required to achieve the final diluted drug concentration. Either remove excess 5% Dextrose Injection, USP from a prefilled intravenous bag or add the calculated volume of 5% Dextrose Injection, USP to a sterile empty intravenous bag. Then add the calculated dose volume of ELAHERE to the intravenous bag.
  
• Gently mix the diluted drug solution by slowly inverting the bag several times to assure uniform mixing. Do not shake or agitate. 

  • If the diluted infusion solution is not used immediately, store solution either at ambient temperature [(18°C to 25°C (64.4°F to 77°F)] for no more than 8 hours (including infusion time), or under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. If refrigerated, allow the infusion bag to reach room temperature prior to administration. After refrigeration, administer diluted infusion solutions within 8 hours (including infusion time).

• Do not freeze prepared infusion solution.

Administration

• Inspect the ELAHERE intravenous infusion bag visually for particulate matter and discoloration prior to administration.
  
• Administer pre-medications prior to ELAHERE administration [see Premedication and Prophylactic Regimen ( 2.3)].
  
• Administer ELAHERE as an intravenous infusion only, using a 0.2 or 0.22 µm polyethersulfone (PES) in-line filter. Do not substitute other membrane materials.
  
• Administer the initial dose as an intravenous infusion at the rate of 1 mg/min. If well tolerated after 30 minutes at 1 mg/min, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.
  
• If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/min, as tolerated.
  
• Following the infusion, flush the intravenous line with 5% Dextrose Injection, USP to ensure delivery of the full dose. Do not use any other intravenous fluids for flushing.

8.1 Pregnancy

Risk Summary

Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells [see Clinical Pharmacology ( 12.1), Nonclinical Toxicology ( 13.1)]. Human immunoglobulin G (IgG) is known to cross the placental barrier; therefore, ELAHERE has the potential to be transmitted from the mother to the developing fetus. There are no available human data on ELAHERE use in pregnant women to inform a drug-associated risk. No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine-gynx. Advise patients of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data: No reproductive or developmental animal toxicity studies have been conducted with mirvetuximab soravtansine-gynx. The cytotoxic component of ELAHERE, DM4, disrupts microtubule function, is genotoxic, and can be toxic to actively dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.

8.2 Lactation

Risk Summary

There are no data on the presence of mirvetuximab soravtansine-gynx in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.

8.3 Females and Males of Reproductive Potential

ELAHERE can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1)].

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating ELAHERE.

Contraception

Females: Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.

8.4 Pediatric Use

Safety and effectiveness of ELAHERE have not been established in pediatric patients.

8.5 Geriatric Use

Of the 682 patients with epithelial ovarian cancer who were treated with ELAHERE across studies, 44% of patients were ≥65 years old. Grade ≥3 adverse reactions occurred in 51% of patients ≥65 years and in 45% <65 years. No clinically meaningful differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.

Age does not have a clinically meaningful effect on the pharmacokinetics of ELAHERE [see Clinical Pharmacology ( 12.3)].

8.6 Renal Impairment

No dosage adjustment of ELAHERE is recommended for patients with mild to moderate renal impairment (CLcr 30 to 89 mL/min). The effect of severe renal impairment (CLcr 15 to < 30 mL/min) or end-stage renal disease on ELAHERE is unknown [see Clinical Pharmacology ( 12.3)].

8.7 Hepatic Impairment

Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

No dosage adjustment of ELAHERE is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST) [see Clinical Pharmacology ( 12.3)].