EMRELIS

1 INDICATIONS AND USAGE EMRELIS is indicated for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test [see Dosage and Administration ( 2.1 )] , who have received a prior systemic therapy . This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) [see Clinical Studies ( 14 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). EMRELIS is a c-Met-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy. ( 1 ) This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )

2 DOSAGE AND ADMINISTRATION For intravenous infusion only. ( 2.5 ) The recommended dosage of EMRELIS is 1.9 mg/kg administered intravenously every 2 weeks until disease progression or unacceptable toxicity. ( 2.2 ) Reconstitute and further dilute EMRELIS prior to intravenous infusion. ( 2.5 ) 2.1 Patient Selection Select patients for treatment with EMRELIS based on the presence of high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining] in patients with non-squamous NSCLC [see Indications and Usage ( 1 ) and Clinical Studies ( 14 )] . Information on FDA-approved tests for the detection of high c-Met protein overexpression is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage of EMRELIS is 1.9 mg/kg (up to a maximum of 190 mg for patients greater than or equal to 100 kg) administered as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. 2.3 Dosage Modifications for Adverse Reactions The recommended dose reductions for adverse reactions are provided in Table 1. Table 1. Recommended Dose Reductions Dose Reduction Recommended Dosage First 1.6 mg/kg every 2 weeks Second 1.3 mg/kg every 2 weeks Third 1 mg/kg every 2 weeks Permanently discontinue EMRELIS in patients who are unable to tolerate 1 mg/kg. The recommended dosage modifications of EMRELIS for adverse reactions are provided in Table 2. Table 2. EMRELIS Dosage Modifications and Management for Adverse Reactions Adverse Reaction Severity a Dosage Modification Peripheral Neuropathy [see Warnings and Precautions ( 5.1 )] Grade 2 or 3 Withhold EMRELIS until recovery to Grade ≤1. Resume EMRELIS at the next lower dose level. Grade 4 Permanently discontinue EMRELIS. Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions ( 5.2 )] Grade 1 Withhold EMRELIS and consider corticosteroids as soon as ILD/pneumonitis is suspected. Resume EMRELIS upon radiographic resolution. Grade ≥2 Permanently discontinue EMRELIS. Keratitis [see Warnings and Precautions ( 5.3 )] Grade 2 Withhold EMRELIS. Refer patients to an eye care professional for an ophthalmic examination and treatment (e.g., lubricating and/or steroidal eye drops). Resume EMRELIS at the same dose at the discretion of the healthcare provider. Grade 3 or 4 Refer patients to an eye care professional for an ophthalmic examination and treatment (e.g., lubricating and/or steroidal eye drops). Permanently discontinue EMRELIS. Infusion-Related Reactions (IRR) [see Warnings and Precautions ( 5.4 )] Grade 1-3 Interrupt EMRELIS infusion and administer supportive treatment. Resume the infusion at a 50% rate reduction. Increase infusion rate as tolerated for subsequent doses. For patients who experience an IRR, administer premedications prior to all future doses (see Table 3 ). Grade 4 Permanently discontinue EMRELIS. Administer supportive treatment. Peripheral Edema [see Adverse Reactions ( 6.1 )] Grade ≥2 First occurrence Withhold EMRELIS until recovery to Grade ≤1. Resume EMRELIS at the same dose level. Subsequent occurrence Withhold EMRELIS until recovery to Grade ≤1. Resume EMRELIS at the next lower dose level. Other Adverse Reactions [see Adverse Reactions ( 6.1 )] Grade 3 First occurrence Withhold EMRELIS until recovery to Grade ≤1. Resume EMRELIS at the same dose. Subsequent occurrence Withhold EMRELIS until recovery to Grade ≤1. Resume EMRELIS at the next lower dose level. Grade 4 Permanently discontinue EMRELIS. a Adverse reactions were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 2. 4 Recommended Premedications for Patients Who Experience Infusion-Related Reactions Table 3 contains the recommended premedications for patients who experience infusion-related reactions to EMRELIS, for subsequent infusions. Table 3: Recommended Premedications for Patients Who Experience Infusion-Related Reactions Medication Class E xamples or equi …

3 DOSAGE FORMS AND STRENGTHS For injection: 20 mg or 100 mg of telisotuzumab vedotin-tllv as a white to off-white, lyophilized powder in a single-dose vial for reconstitution and further dilution. For injection: 20 mg or 100 mg of telisotuzumab vedotin-tllv as a lyophilized powder in a single-dose vial. ( 3 )

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Peripheral Neuropathy [see Warnings and Precautions ( 5.1 )] Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions ( 5.2 )] Ocular Surface Disorders [see Warnings and Precautions ( 5.3 )] Infusion-Related Reactions (IRR) [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. LUMINOSITY The safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to EMRELIS in 168 patients with locally advanced or metastatic EGFR wild-type non-squamous NSCLC with c-Met protein overexpression who received EMRELIS as a single agent administered at 1.9 mg/kg intravenously every 2 weeks in the LUMINOSITY study [see Clinical Studies ( 14 )]. Among patients who received EMRELIS, 42% were exposed for 6 months or longer and 11% were exposed for greater than one year. The median age of patients who received EMRELIS was 64.5 years (range: 33 to 83 years); 70% were male; 65% were White; 1.8% were Black or African American, 33% were Asian; and 0.6% were of Hispanic or Latino ethnicity. Serious adverse reactions occurred in 35% of patients. Serious adverse reactions occurring in ≥2% of patients included ILD/pneumonitis (5%), pneumonia (5%), peripheral neuropathy (3.6%), and pleural effusion (2.4%). Fatal adverse reactions occurred in 5% of patients who received EMRELIS, including ILD/pneumonitis (1.8%), pneumonia (1.2%), sudden death (1.2%), noninfectious endocarditis (0.6%) and myocardial infarction (0.6%). Permanent discontinuations of EMRELIS due to adverse reactions occurred in 30% of patients. Adverse reactions which resulted in permanent discontinuation of EMRELIS in ≥2% included peripheral neuropathy and ILD/pneumonitis. Dosage interruptions due to adverse reactions occurred in 44% of patients. Adverse reactions which required dosage interruption in ≥2% of patients included peripheral neuropathy, fatigue, pneumonia, increased ALT, blurred vision, COVID-19, ILD/pneumonitis, and keratitis. Dose reductions due to adverse reactions occurred in 28% of patients. Adverse reactions which required dose reductions in ≥2% of patients included peripheral neuropathy, fatigue, and keratitis. The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased ALT, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium. Table 5 summarizes the adverse reactions in LUMINOSITY. Table 5. Adverse Reactions (≥10%) in Patients with EGFR Wild-Type Non-squamous NSCLC with c-Met Protein Overexpression in LUMINOSITY Adverse Reaction EMRELIS (N=168) All Grades 1 % Grade 3 or 4 1 % Nervous system disorders Peripheral neuropathy 2 51 11 General disorders and administration site conditions Fatigue 2 29 3.6 Peripheral edema 2 22 1.8 Metabolism and nutrition disorders Decreased appetite 22 0.6 Gastrointestinal disorders Nausea 15 0 Constipation 14 0.6 Vomiting 10 0.6 Eye disorders Blurred vision 3 …

7 DRUG INTERACTIONS S trong CYP3A I nhibitors : concomitant use with EMRELIS may increase the AUC of MMAE. Monitor for increased risk of adverse reactions to EMRELIS. ( 7.1 ) 7.1 Effect of Other Drugs on EMRELIS Strong CYP3A Inhibitors Concomitant use with strong CYP3A inhibitors may increase unconjugated MMAE AUC [see Clinical Pharmacology ( 12.3 ) ] , which may increase the risk of EMRELIS adverse reactions. Monitor patients for adverse reactions when EMRELIS is given concomitantly with strong CYP3A inhibitors.

8 USE IN SPECIFIC POPULATIONS Severe or Moderate Hepatic I mpairment : Avoid use of EMRELIS. ( 8.6 ) Lactation : Advise not to breastfeed. ( 8.2 ) Infertility : May impair fertility. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on the mechanism of action and findings in animals, EMRELIS can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available human data on EMRELIS use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of EMRELIS, MMAE, to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural abnormalities at exposures similar to the clinical exposure at the recommended dose [see Data ] . Advise patients of the potential risks to a fetus. 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. Data Animal Data No embryo-fetal development studies in animals have been performed with telisotuzumab vedotin-tllv. In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of EMRELIS, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, agnathia, malrotated limbs, and gastroschisis compared to controls at a dose of 0.2 mg/kg (approximately 2 times the human area under the curve [AUC] at the recommended dose). 8.2 Lactation Risk Summary There are no data on the presence of telisotuzumab vedotin-tllv or MMAE in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with EMRELIS and for 1 month after the last dose. 8.3 Females and Males of Reproductive Potential EMRELIS can cause 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 EMRELIS treatment. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with EMRELIS and for 2 months after the last dose. Males Based on genotoxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment with EMRELIS and for 4 months after the last dose. Infertility Females Based on findings in animal studies with MMAE-containing antibody-drug conjugates (ADCs), EMRELIS may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology ( 13.1 )] . Males Based on findings from animal studies, EMRELIS may impair male fertility. The reversibility of this effect is unknown [see Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use Safety and effectiveness of EMRELIS have not been established in pediatric patients. 8.5 Geriatric Use Of the 168 patients with previously treated EGFR wild-type non-squamous NSCLC with c-Met protein overexpression treated with EMRELIS in LUMINOSITY, 50% were ≥65 years of age and 12% were ≥75 years of age. No overall differences in safety or effectiveness were observed between older and younger patients. 8.6 Hepatic Impairment Avoid use of EMRELIS in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and any AST). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. EMRELIS has not been studied in patients with moderate or severe hepatic impairment. No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >ULN and ≤1.5 x ULN and any AST) [see Clinical Pharmacology ( 12.3 ) ] .

12.1 Mechanism of Action Telisotuzumab vedotin-tllv is a c-Met-directed antibody drug conjugate (ADC). The antibody is a humanized IgG1κ directed against c-Met, the cell surface receptor for hepatocyte growth factor. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease cleavable linker. Following binding to c-Met-expressing cells, telisotuzumab vedotin-tllv undergoes internalization and intracellular cleavage of MMAE. MMAE disrupts the microtubule network of actively dividing cells, subsequently inducing cell cycle arrest and apoptotic cell death. Telisotuzumab vedotin-tllv exhibited antitumor activity in xenograft models of NSCLC.

11 DESCRIPTION Telisotuzumab vedotin-tllv is a c-Met directed antibody-drug conjugate (ADC) comprised of a humanized immunoglobulin G1 kappa (IgG1κ) monoclonal antibody conjugated to the small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), via a protease-cleavable valine-citrulline (vc) linker. The antibody is produced in a mammalian cell line (Chinese hamster ovary) and the drug-linker is produced by chemical synthesis. Each monoclonal antibody molecule carries an average of 3 MMAE molecules. Telisotuzumab vedotin-tllv has an approximate molecular weight of 152 kDa. EMRELIS (telisotuzumab vedotin-tllv) for injection is a sterile, white to off-white, preservative-free, lyophilized powder in a single-dose vial for reconstitution and dilution prior to intravenous infusion. EMRELIS is supplied as 20 mg per vial or 100 mg per vial and requires reconstitution with Sterile Water for Injection, USP (1.1 mL and 5.2 mL, respectively) to obtain a concentration of 20 mg/mL [see Dosage and Administration ( 2.4 )] . Following reconstitution, each mL delivers 20 mg of telisotuzumab vedotin-tllv, and histidine (2.33 mg), polysorbate 80 (0.10 mg), sucrose (70.0 mg), and Water for Injection. Hydrochloric acid was added to adjust the pH to 6.0. Telisotuzumab vedotin-tllv is a c-Met directed antibody-drug conjugate (ADC) comprised of a humanized immunoglobulin G1 kappa (IgG1κ) monoclonal antibody conjugated to the small molecule microtubule-disrupting agent, monomethyl auristatin E (MMAE), via a protease-cleavable valine-citrulline (vc) linker. The antibody is produced in a mammalian cell line (Chinese hamster ovary) and the drug-linker is produced by chemical synthesis. Each monoclonal antibody molecule carries an average of 3 MMAE molecules. Telisotuzumab vedotin-tllv has an approximate molecular weight of 152 kDa.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied EMRELIS (telisotuzumab vedotin-tllv) for injection is a sterile, preservative-free, white to off-white lyophilized powder, supplied in a glass single-dose vial. Carton of one 20 mg/vial (NDC 0074-1044-01) Carton of one 100 mg/vial (NDC 0074-1055-01) Storage and Handling Store refrigerated at 2 o C to 8 o C (36 o F to 46 o F) in original carton to protect from light. Do not freeze. Do not shake. Special Handling EMRELIS is a hazardous product. Follow special handling and disposal procedures. 1