TECVAYLI

Boxed Warnings 8/2025 Indications and Usage ( 1 ) 3/2026 Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 , 2.6 ) 3/2026 Warnings and Precautions ( 5.1 , 5.2 , 5.3 , 5.4 , 5.5 , 5.6 , 5.7 ) 3/2026

1 INDICATIONS AND USAGE TECVAYLI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. TECVAYLI is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma: in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent ( 1 ). as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody ( 1 ).

2 DOSAGE AND ADMINISTRATION For subcutaneous injection only. ( 2.1 ) Patients should be hospitalized for 48 hours after administration of both step-up dose 1 and step-up dose 2. Instruct patients to remain within proximity of a healthcare facility and monitored daily for 48 hours after the first treatment dose within the TECVAYLI step-up dosing schedule. ( 2.1 ) See Full Prescribing Information for the recommended dosage for TECVAYLI monotherapy and combination therapy. ( 2.2 , 2.3 ) Administer pretreatment medications as recommended. ( 2.3 ) Refer to Tables 8, 9, 10, and 11 to determine the total dose, injection volume, and number of vials based on the patient's body weight. ( 2.6 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) 2.1 Important Dosage and Administration Information TECVAYLI is for subcutaneous injection only. Administer pretreatment medications prior to each dose of the TECVAYLI step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose as described in Tables 1 and 2 [see Dosage and Administration (2.3) ] . Administer TECVAYLI subcutaneously according to the step-up dosing schedule in Tables 1 and 2 to reduce the incidence and severity of cytokine release syndrome (CRS). Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of both step-up dose 1 and step-up dose 2. Instruct patients to remain within proximity of a healthcare facility and monitor them daily for 48 hours after the first treatment dose within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.5) and Warnings and Precautions (5.1 , 5.2) ] . Refer to Tables 8, 9, 10, and 11 to determine the dosage based on predetermined weight ranges [see Dosage and Administration (2.6) ] . 2.2 Recommended TECVAYLI Dosage In Combination with Daratumumab and Hyaluronidase-fihj The recommended dosing schedule for TECVAYLI in combination with subcutaneous daratumumab and hyaluronidase-fihj is provided in Table 1. TECVAYLI should be administered until disease progression or unacceptable toxicity. Table 1: TECVAYLI Dosage Schedule in Combination with Daratumumab and Hyaluronidase-fihj Dosing schedule Week/Day TECVAYLI Dosage See Table 3 for recommendations on restarting TECVAYLI after dose delays. Concomitant Therapy Day 0 N/A Daratumumab and hyaluronidase-fihj Step-up dosing schedule The Step-up dosing schedule is a component of the recommended TECVAYLI dosage but is not applicable for the daratumumab and hyaluronidase-fihj dosing. Day 1 Step-up dose 1 (0.06 mg/kg) Step-up dose 1 must be administered 20 hours or more after the daratumumab and hyaluronidase-fihj dose. N/A Day 3 Step-up dose 2 (0.3 mg/kg) Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and if adverse reactions occur, step-up dose 2 may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions. N/A Day 7 First treatment dose (1.5 mg/kg) First treatment dose (1.5 mg/kg) may be given between 2 to 4 days after step-up dose 2 and if adverse reactions occur, first full treatment dose may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions. , Administer TECVAYLI at least 3 hours after the daratumumab and hyaluronidase-fihj dose for the first treatment dose. For subsequent doses, administer TECVAYLI at least 15 minutes after the daratumumab and hyaluronidase-fihj dose. Daratumumab and hyaluronidase-fihj Weekly dosing schedule Weeks 2 to 8 1.5 mg/kg once weekly , Maintain a minimum of 5 days between 1.5 mg/kg once weekly doses. Daratumumab and hyaluronidase-fihj once weekly Biweekly (every two weeks) dosing schedule Weeks 9 to 24 3 mg/kg every two weeks , Maintain a minimum of 12 days between 3 mg/kg every two weeks doses. Daratumumab and hyaluronidase-fihj every two weeks Every four weeks dosing schedule Week 25 onwards 3 mg/kg every four weeks …

3 DOSAGE FORMS AND STRENGTHS Injection 30 mg/3 mL (10 mg/mL) clear to slightly opalescent, colorless to light yellow solution in a single-dose vial. 153 mg/1.7 mL (90 mg/mL) clear to slightly opalescent, colorless to light yellow solution in a single-dose vial. Injection 30 mg/3 mL (10 mg/mL) in a single-dose vial ( 3 ) 153 mg/1.7 mL (90 mg/mL) in a single-dose vial ( 3 )

4 CONTRAINDICATIONS None. None. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are also described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity including ICANS [see Warnings and Precautions (5.2) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Neutropenia [see Warnings and Precautions (5.6) ] Hypersensitivity and Other Administration Reactions [see Warnings and Precautions (5.7) ] The most common adverse reactions (≥20%) in patients who received TECVAYLI monotherapy are pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. ( 6.1 ) The most common adverse reactions (≥20%) in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj are hypogammaglobulinemia, upper respiratory tract infection, cytokine release syndrome, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis and weight decreased. ( 6.1 ) The most common Grade 3 to 4 laboratory abnormalities (≥20%) with TECVAYLI (as monotherapy or in combination with daratumumab and hyaluronidase-fihj) are decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 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. Relapsed/Refractory Multiple Myeloma In Combination with Daratumumab and Hyaluronidase-fihj The safety of TECVAYLI in combination with daratumumab and hyaluronidase-fihj (N=283) compared with either daratumumab and hyaluronidase-fihj, pomalidomide and dexamethasone (DPd) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) (N=290) was evaluated in patients with relapsed or refractory multiple myeloma in MajesTEC-3 [see Clinical Studies (14.1) ] . Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg once weekly, followed by TECVAYLI 3 mg/kg every two weeks, followed by TECVAYLI 3 mg/kg every four weeks, subcutaneously. Among patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj the median exposure was 32 (range 0.03 to 43) months. Among patients who received DPd or DVd the median exposure was 16 (range 0.03 to 45) months. Serious adverse reactions occurred in 71% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj. Serious adverse reactions reported in ≥3% of patients included pneumonia (33%), upper respiratory tract infection (15%), cytokine release syndrome (10%), COVID-19 (7%), sepsis (6%), second primary malignancy (5%), pyrexia (4.9%), febrile neutropenia (4.6%), and gastroenteritis (4.2%). Fatal adverse reactions occurred in 2.5% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj, and included sepsis (0.7%), pneumonia (0.4%), sudden death (0.4%), myocardial infarction (0.4%), enterovirus myocarditis (0.4%) and hemophagocytic lymphohistiocytosis (0.4%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 6% of patients. Adverse reactions leading to discontinuation of TECVAYLI in more than one patient were pneumonia (1.1%), diarrhea (0.7%), fatigue (0.7%), second primary malignancy (0.7%), upper respiratory tract infection (0.7%) and cough (0.7%). Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 94% of patients. Adverse reactions which required dosage interruption of TECVAYLI in ≥5% of pati …

7 DRUG INTERACTIONS TECVAYLI causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of certain cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates, which may increase the risk of adverse reactions of the CYP substrates. The highest risk of drug-drug interaction is expected to occur after initiation of TECVAYLI step-up dosing schedule up to 7 days after the first treatment dose and during and after CRS [see Warnings and Precautions (5.1) ] . Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate as needed. Certain CYP Substrates : Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate, as needed ( 7 ).

8 USE IN SPECIFIC POPULATIONS Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on the mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TECVAYLI in pregnant patients to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with TECVAYLI. Teclistamab-cqyv causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, teclistamab-cqyv has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. TECVAYLI is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered. 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. 8.2 Lactation Risk Summary There are no data on the presence of teclistamab-cqyv in human milk, the effect on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to TECVAYLI are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TECVAYLI and for 5 months after the last dose. 8.3 Females and Males of Reproductive Potential TECVAYLI may cause fetal harm when administered to a pregnant patient [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating TECVAYLI. Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 5 months after the last dose of TECVAYLI. 8.4 Pediatric Use The safety and efficacy of TECVAYLI have not been established in pediatric patients. 8.5 Geriatric Use Of the 165 patients with relapsed or refractory multiple myeloma treated with TECVAYLI in MajesTEC-1 at the recommended dosage, 48% were 65 years of age or older, and 15% were 75 years of age or older. No overall differences in safety or effectiveness were observed between patients 65 to 74 years of age compared to younger patients. The study did not include a sufficient number of patients 75 years of age or older to assess whether there are differences in safety or effectiveness. Of the 291 patients with relapsed or refractory multiple myeloma treated with TECVAYLI at the recommended dosage in combination with daratumumab and hyaluronidase-fihj in MajesTEC-3, 51% were younger than 65 years of age, 39% were 65 to 74 years of age, and 11% were 75 years of age or older. No overall differences in effectiveness were observed between patients 65 to 74 years of age compared to younger patients. The study did not include a sufficient number of patients 75 years of age or older to assess whether there are differences in effectiveness compared to younger patients. There was a higher incidence of serious adverse reactions in patients 75 years of age or older (83%) and in patients 65 to 74 years of age (77%) as compared to patients younger than 65 years of age (63%).

12.1 Mechanism of Action Teclistamab-cqyv is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In vitro , teclistamab-cqyv activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells.

11 DESCRIPTION Teclistamab-cqyv, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is a humanized immunoglobulin G4-proline, alanine, alanine (IgG4-PAA) antibody. Teclistamab-cqyv is produced in Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. Teclistamab-cqyv consists of an anti-BCMA heavy chain and light chain and an anti-CD3 heavy chain and light chain with two interchain disulfide bonds connecting the two arms. The molecular weight of teclistamab-cqyv is approximately 146 kDa. TECVAYLI ® (teclistamab-cqyv) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to light yellow solution supplied in a single-dose vial for subcutaneous administration. Each TECVAYLI 3 mL single-dose vial contains 30 mg of teclistamab-cqyv, edetate disodium (0.054 mg), glacial acetic acid (0.72 mg), polysorbate 20 (1.2 mg), sodium acetate (2.7 mg), sucrose (240 mg), and Water for Injection, USP. Each TECVAYLI 1.7 mL single-dose vial contains 153 mg of teclistamab-cqyv, edetate disodium (0.031 mg), glacial acetic acid (0.41 mg), polysorbate 20 (0.68 mg), sodium acetate (1.5 mg), sucrose (140 mg), and Water for Injection, USP.

16 HOW SUPPLIED/STORAGE AND HANDLING TECVAYLI ® (teclistamab-cqyv) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to light yellow solution supplied as follows: One 30 mg/3 mL (10 mg/mL) single-dose vial in a carton: NDC: 57894-449-01 One 153 mg/1.7 mL (90 mg/mL) single-dose vial in a carton: NDC: 57894-450-01 Store refrigerated at 2 °C to 8 °C (36 °F to 46 °F) in the original carton to protect from light. Do not freeze.