ELAHERE

Dosage and Administration ( 2.5 ) 07/2025

1 INDICATIONS AND USAGE ELAHERE ® is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test [see Dosage and Administration ( 2.1 )]. ELAHERE is a folate receptor alpha (FRα)-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. ( 1 , 2.1 )

2 DOSAGE AND ADMINISTRATION Administer ELAHERE as an intravenous infusion only after dilution in 5% Dextrose Injection, USP. ELAHERE is incompatible with normal saline. ( 2.5 ) The recommended dose of ELAHERE is 6 mg/kg adjusted ideal body weight administered as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. ( 2.2 ) Premedicate with a corticosteroid, antihistamine, and antipyretic. ( 2.3 ) Premedicate with an antiemetic, ophthalmic topical steroids, and lubricating eye drops. ( 2.3 , 5.1 ) See full Prescribing Information for preparation and administration instructions and dose modifications for adverse reactions. ( 2 ) 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 Premedica tion 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. Table 1: Premedication Prior to Each ELAHERE Infusion Premedication Route of Administration Examples (or equivalent) Administration Time Prior to ELAHERE Infusion Corticosteroid intravenous dexamethasone 10 mg Antihistamine oral or intravenous diphenhydramine 25 mg to 50 mg At least 30 minutes prior Antipyretic oral or intravenous acetaminophen 325 mg to 650 mg Antiemetic oral or intravenous 5-HT 3 serotonin receptor antagonist or appropriate alternatives Before each dose and thereafter as needed Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs. Ophthalmic Exams and Premedication Ophthalmic E xam : 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. Table 2: Dosage Reduction Schedule ELAHERE Dose Levels First Dose Reduction 5 mg/kg AIBW once every 3 weeks (21-day cycle) Second Dose Reduction 4 mg/kg AIBW once every 3 weeks (21-day cycle) * * Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW. T …

3 DOSAGE FORMS AND STRENGTHS Injection: 100 mg/20 mL (5 mg/mL) clear to slightly opalescent, colorless solution in a single-dose vial. Injection: 100 mg/20 mL (5 mg/mL) in a single-dose vial. ( 3 )

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: Ocular Disorders [see Warnings and Precautions ( 5.1 )] . Pneumonitis [see Warnings and Precautions ( 5.2 )] . Peripheral Neuropathy [see Warnings and Precautions ( 5.3 )] . The most common (≥20 %) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-633-9110 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. The pooled safety population described in Warnings and Precautions reflect exposure to ELAHERE in 682 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer at 6 mg/kg AIBW administered intravenously once every 3 weeks until disease progression or unacceptable toxicity in Study 0416, Study 0417, Study 0403 (NCT02631876), and Study 0401 (NCT01609556). The median duration of treatment was 4.4 months (range: 1.0 to 30.0). In the pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils. Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Study 0416 The safety of ELAHERE was evaluated in Study 0416, a multicenter, open-label, active-controlled, randomized, two-arm, study in patients (n=453) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer [see Clinical Studies ( 14 )] . Patients received ELAHERE 6 mg/kg AIBW once every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment was 5 months (range: 0.69 to 27.4). Serious adverse reactions occurred in 24% of patients treated with ELAHERE. The most common (≥2%) serious adverse reactions were intestinal obstruction (5%), abdominal pain (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 3% of patients, including intestinal obstruction, dyspnea in the setting of subileus, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke, and pulmonary embolus. Permanent discontinuation of ELAHERE due to adverse reactions occurred in 9% of patients. The most common (≥1%) adverse reactions leading to permanent discontinuation were pneumonitis (2%), blurred vision (1%), and peripheral neuropathy (1%). Dosage delays of ELAHERE due to an adverse reaction occurred in 54% of patients treated with ELAHERE. Adverse reactions which required dosage delays in ≥3% of patients included blurred vision (22%), keratopathy (19%), dry eye (7%), neutropenia (6%), pneumonitis (6%), photophobia (5%), cataract (4%), and peripheral neuropathy (4%). Dose reductions of ELAHERE due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dose reductions in ≥3% of patients included blurred vision (14%), keratopathy (10%), peripheral neuropathy (6%), and dry eye (5%). Tables 4 and 5 summarize adve …

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Closely monitor for ELAHERE adverse reactions. ( 7.1 ) 7.1 Effects of Other Drugs on ELAHERE Strong CYP3A4 Inhibitors DM4 is a CYP3A4 substrate. Concomitant use of ELAHERE with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of ELAHERE adverse reactions [see Adverse Reactions ( 6 )] . Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors [ see Warnings and Precautions ( 5 ) ] .

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Moderate or severe hepatic impairment: Avoid use. ( 8.7 ) 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% 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 )] .

12.1 Mechanism of Action Mirvetuximab soravtansine-gynx is an antibody-drug conjugate (ADC). The antibody is a chimeric IgG1 directed against folate receptor alpha (FRα). The small molecule, DM4, is a microtubule inhibitor attached to the antibody via a cleavable linker. Upon binding to FRα, mirvetuximab soravtansine-gynx is internalized followed by intracellular release of DM4 via proteolytic cleavage. DM4 disrupts the microtubule network within the cell, resulting in cell cycle arrest and apoptotic cell death.

11 DESCRIPTION Mirvetuximab soravtansine-gynx is a folate receptor alpha (FRα)-directed antibody-drug conjugate (ADC) consisting of three components: 1) an anti-FRα monoclonal antibody of IgG1 subtype 2) the small molecule anti-tubulin agent DM4 (a maytansine derivative) and 3) a linker, sulfo-SPDB (1-(2,5-dioxopyrrolidin-1-yl)oxy-1-oxo-4-(pyridin-2-yldisulfanyl)butane-2-sulfonic acid) that covalently attaches DM4 to the mirvetuximab antibody. Mirvetuximab soravtansine-gynx has an approximate molecular weight of 150 kDa. An average of 3.4 molecules of DM4 are attached to each antibody molecule. Mirvetuximab soravtansine-gynx is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis. Mirvetuximab soravtansine-gynx has the following structure: ELAHERE (mirvetuximab soravtansine-gynx) injection is supplied as a sterile, preservative-free, clear to slightly opalescent, colorless solution containing 100 mg/20 mL of mirvetuximab soravtansine-gynx in single-dose vials. Each mL of solution contains 5 mg of mirvetuximab soravtansine-gynx, and glacial acetic acid (0.22 mg), polysorbate 20 (0.1 mg), sodium acetate (0.53 mg), sucrose (90 mg), and Water for Injection. The pH is approximately 5.0. The ELAHERE vial stoppers are not made with natural rubber latex. Mirvetuximab soravtansine-gynx has the following structure:

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Each ELAHERE (mirvetuximab soravtansine-gynx) injection carton (NDC 72903-853-01) contains: One single-dose vial containing 100 mg of mirvetuximab soravtansine-gynx in 20 mL (5 mg/mL) of clear to slightly opalescent, colorless sterile solution. Storage and Handling Store ELAHERE vials upright in a refrigerator at 2°C to 8°C (36°F to 46°F) until the time of preparation in the original carton to protect from light. Do not freeze or shake. ELAHERE is a hazardous drug. Follow applicable special handling and disposal procedures 1 .