TECVAYLI

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.

TECVAYLI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate [see Clinical Studies (14) ] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 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 who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )

TECVAYLI Recommended Dosing Schedule ( 2.1 ) Dosing Schedule Day Dose All Patients Step-up Dosing Schedule Day 1 Step-up dose 1 0.06 mg/kg Day 4 Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions. Step-up dose 2 0.3 mg/kg Day 7 First treatment dose may be given between 2 to 4 days after step-up dose 2 and may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions. First treatment dose 1.5 mg/kg Weekly Dosing Schedule One week after first treatment dose and weekly thereafter Subsequent treatment doses 1.5 mg/kg once weekly Patients who have achieved and maintained a complete response or better for a minimum of 6 months Biweekly (every two weeks) dosing schedule The dosing frequency may be decreased to 1.5 mg/kg every two weeks For subcutaneous injection only. ( 2.1 ) Patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule. ( 2.1 ) Administer pretreatment medications as recommended. ( 2.2 ) Refer to Tables 7, 8, and 9 to determine the dosage based on predetermined weight ranges. ( 2.5 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.5 ) 2.1 Recommended Dosage For subcutaneous injection only. The recommended dosing schedule for TECVAYLI is provided in Table 1. The recommended dosage of TECVAYLI is step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity. In patients who have achieved and maintained a complete response or better for a minimum of 6 months, the dosing frequency may be decreased to 1.5 mg/kg every two weeks until disease progression or unacceptable toxicity. 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 Table 1 [see Dosage and Administration (2.2) ] . Administer TECVAYLI subcutaneously according to the step-up dosing schedule in Table 1 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 all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.4) and Warnings and Precautions (5.1 , 5.2) ] . Table 1: TECVAYLI Dosing Schedule Dosing schedule Day Dose All Patients Step-up dosing schedule See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. Day 1 Step-up dose 1 0.06 mg/kg Day 4 Step-up dose 2 may be given between 2 to 4 days after step-up dose 1 and may be given up to 7 days after step-up dose 1 to allow for resolution of adverse reactions. Step-up dose 2 0.3 mg/kg Day 7 First treatment dose may be given between 2 to 4 days after step-up dose 2 and may be given up to 7 days after step-up dose 2 to allow for resolution of adverse reactions. First treatment dose 1.5 mg/kg Weekly dosing schedule One week after first treatment dose and weekly thereafter Subsequent treatment doses 1.5 mg/kg once weekly Patients who have achieved and maintained a complete response or better for a minimum of 6 months Biweekly (every two weeks) dosing schedule The dosing frequency may be decreased to 1.5 mg/kg every two weeks. Refer to Tables 7, 8, and 9 to determine the dosage based on predetermined weight ranges [see Dosage and Administration (2.5) ] . 2.2 Recommended Pretreatment Medications Administer the following pretreatment medications 1 to 3 hours before each dose of the TECVAYLI step-up dosing schedule, which includes step-up dose 1, step-up dose 2, and the first treatment dose (see Table 1 ), to reduce the risk of CRS [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . Corticosteroid (oral or intravenous dexamethasone 16 mg) Histamine-1 (H1) receptor antagonist (oral or intravenous diphenhydramine 50 mg or equivalent) Antipyretics (oral or intravenous acetaminophen 650 mg to 1,000 mg or equivalent) Administration of pretreatment medications may be required prior to administration of subsequent doses of TECVAYLI in the following patients: Patients who repeat doses within the TECVAYLI step-up dosing schedule following a dose delay [see Dosage and Administration (2.3) ]. Patients who experienced CRS following the prior dose of TECVAYLI [see Dosage and Administration (2.4) ]. Prophylaxis for Herpes Zoster Reactivation Prior to starting treatment with TECVAYLI, consider initiation of antiviral prophylaxis to prevent herpes zoster reactivation per guidelines. 2.3 Restarting TECVAYLI after Dosage Delay If a dose of TECVAYLI is delayed, restart therapy based on the recommendations in Table 2 and resume the treatment schedule accordingly [see Dosage and Administration (2.1) ] . Administer pretreatment medications as indicated in Table 2 . Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.4) and Warnings and Precautions (5.1 , 5.2) ]. Table 2: Recommendations for Restarting Therapy with TECVAYLI After Dose Delay Last dose administered Time since the last dose administered Action Step-up dose 1 More than 7 days Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Administer pretreatment medications prior to TECVAYLI dose and monitor patients accordingly [see Dosage and Administration (2.2, 2.5)]. Step-up dose 2 8 days to 28 days Repeat step-up dose 2 (0.3 mg/kg) and continue TECVAYLI step-up dosing schedule. More than 28 days Consider benefit-risk of restarting TECVAYLI in patients who require a dose delay of more than 28 days due to an adverse reaction. Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Any weekly treatment dose 28 days or less Continue TECVAYLI at last treatment dose in weekly schedule (1.5 mg/kg once weekly; see Table 1 ). 29 days to 56 days Restart TECVAYLI step-up dosing schedule at step-up dose 2 (0.3 mg/kg). More than 56 days Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). Any biweekly (every two weeks) treatment dose 63 days or less Continue TECVAYLI at last treatment dose in biweekly schedule (1.5 mg/kg every two weeks; see Table 1 ). 64 days to 112 days Restart TECVAYLI step-up dosing schedule at step up dose 2 (0.3 mg/kg). More than 112 days Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). 2.4 Dosage Modifications for Adverse Reactions Dosage reductions of TECVAYLI are not recommended. Dosage delays may be required to manage toxicities related to TECVAYLI [see Warnings and Precautions (5) ]. See Tables 3 , 4 , and 5 for recommended actions for adverse reactions of CRS, neurologic toxicity, and ICANS. See Table 6 for recommended actions for other adverse reactions following administration of TECVAYLI. Management of CRS, Neurologic Toxicity and ICANS Cytokine Release Syndrome (CRS) Management recommendations for CRS are summarized in Table 3. Identify CRS based on clinical presentation [see Warnings and Precautions (5.1) ]. Evaluate and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, withhold TECVAYLI until CRS resolves. Manage according to the recommendations in Table 3 and consider further management per current practice guidelines. Administer supportive therapy for CRS, which may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Table 3: Recommendations for Management of Cytokine Release Syndrome Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS. Presenting Symptoms Actions Grade 1 Temperature ≥100.4 °F (38 °C) Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy. Withhold TECVAYLI until CRS resolves. Administer pretreatment medications prior to next dose of TECVAYLI. See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. Grade 2 Temperature ≥100.4 °F (38 °C) with: Hypotension responsive to fluids and not requiring vasopressors, and/or, Oxygen requirement of low-flow nasal cannula Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min. or blow-by. Withhold TECVAYLI until CRS resolves. Administer pretreatment medications prior to next dose of TECVAYLI. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1) ]. Grade 3 Temperature ≥100.4 °F (38 °C) with: Hypotension requiring one vasopressor with or without vasopressin, and/or, Oxygen requirement of high-flow nasal cannula , facemask, non-rebreather mask, or Venturi mask. First Occurrence of Grade 3 CRS with Duration Less than 48 Hours: Withhold TECVAYLI until CRS resolves. Provide supportive therapy, which may include intensive care. Administer pretreatment medications prior to next dose of TECVAYLI. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1) ]. Recurrent Grade 3 CRS or Grade 3 CRS with Duration 48 Hours or Longer: Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care. Grade 4 Temperature ≥100.4 °F (38 °C) with: Hypotension requiring multiple vasopressors (excluding vasopressin), and/or, Oxygen requirement of positive pressure (e.g., continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), intubation, and mechanical ventilation). Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care. Neurologic Toxicity and ICANS Management recommendations for neurologic toxicity and ICANS are summarized in Tables 4 and 5. At the first sign of neurologic toxicity, including ICANS, withhold TECVAYLI and consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide supportive therapy, which may include intensive care, for severe or life-threatening neurologic toxicities, including ICANS [see Warnings and Precautions (5.2) ] . Manage ICANS according to the recommendations in Table 5 and consider further management per current practice guidelines. Table 4: Recommendations for Management of Neurologic Toxicity (excluding ICANS) Adverse Reaction Severity Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. Actions Neurologic Toxicity (excluding ICANS) Grade 1 Withhold TECVAYLI until neurologic toxicity symptoms resolve or stabilize. See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. Grade 2 Grade 3 (First occurrence) Withhold TECVAYLI until neurologic toxicity symptoms improve to Grade 1 or less. Provide supportive therapy. Grade 3 (Recurrent) Grade 4 Permanently discontinue TECVAYLI. Provide supportive therapy, which may include intensive care. Table 5: Recommendations for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome Grade Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS. Presenting Symptoms Management is determined by the most severe event, not attributable to any other cause. Actions Grade 1 ICE score 7–9 If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue" = 1 point); Writing (ability to write a standard sentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points. , or depressed level of consciousness Not attributable to any other cause. : awakens spontaneously. Withhold TECVAYLI until ICANS resolves. See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Grade 2 ICE score 3–6 , or depressed level of consciousness : awakens to voice. Withhold TECVAYLI until ICANS resolves. Administer dexamethasone All references to dexamethasone administration are dexamethasone or equivalent. 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1) ] . Grade 3 ICE score 0–2 , or depressed level of consciousness : awakens only to tactile stimulus, or seizures , either: any clinical seizure, focal or generalized, that resolves rapidly, or non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local edema on neuroimaging . First Occurrence of Grade 3 ICANS: Withhold TECVAYLI until ICANS resolves. Administer dexamethasone 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Patients should be hospitalized for 48 hours following the next dose of TECVAYLI [see Dosage and Administration (2.1) ] . Recurrent Grade 3 ICANS: Permanently discontinue TECVAYLI Administer dexamethasone 10 mg intravenously and repeat dose every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Grade 4 ICE score 0 , or depressed level of consciousness : either: patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, or seizures , either: life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between, or motor findings : deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral edema , with signs/symptoms such as: diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing's triad. Permanently discontinue TECVAYLI. Administer dexamethasone 10 mg intravenously and repeat dose every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. Alternatively, consider administration of methylprednisolone 1,000 mg per day intravenously and continue methylprednisolone 1,000 mg per day intravenously for 2 or more days. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management, including consideration for starting non-sedating, anti-seizure medicines for seizure prophylaxis. Provide supportive therapy, which may include intensive care. Table 6: Recommended Dosage Modifications for Other Adverse Reactions Adverse Reactions Severity Actions Infections Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. [see Warnings and Precautions (5.5) ] All Grades Withhold TECVAYLI in patients with active infection during the step-up dosing schedule. See Table 2 for recommendations on restarting TECVAYLI after dose delays [see Dosage and Administration (2.3)]. Grade 3 Withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until infection improves to Grade 1 or less. Grade 4 Consider permanent discontinuation of TECVAYLI. If TECVAYLI is not permanently discontinued, withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until infection improves to Grade 1 or less. Hematologic Toxicities [see Warnings and Precautions (5.6) and Adverse Reactions (6.1) ] Absolute neutrophil count less than 0.5 × 10 9 /L Withhold TECVAYLI until absolute neutrophil count is 0.5 × 10 9 /L or higher. Febrile neutropenia Withhold TECVAYLI until absolute neutrophil count is 1 × 10 9 /L or higher and fever resolves. Hemoglobin less than 8 g/dL Withhold TECVAYLI until hemoglobin is 8 g/dL or higher. Platelet count less than 25,000/mcL Platelet count between 25,000/mcL and 50,000/mcL with bleeding Withhold TECVAYLI until platelet count is 25,000/mcL or higher and no evidence of bleeding. Other Non-Hematologic Adverse Reactions [see Warnings and Precautions (5.4) and Adverse Reactions (6.1) ] Grade 3 Withhold TECVAYLI until adverse reaction improves to Grade 1 or less. Grade 4 Consider permanent discontinuation of TECVAYLI. If TECVAYLI is not permanently discontinued, withhold subsequent treatment doses of TECVAYLI (i.e., doses administered after TECVAYLI step-up dosing schedule) until adverse reaction improves to Grade 1 or less. 2.5 Preparation and Administration TECVAYLI is intended for subcutaneous use by a healthcare provider only. TECVAYLI should be administered by a healthcare provider with adequate medical personnel and appropriate medical equipment to manage severe reactions, including CRS and ICANS [see Warnings and Precautions (5.1 , 5.2) ] . TECVAYLI is a clear to slightly opalescent, colorless to light yellow solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is discolored, or cloudy, or if foreign particles are present. TECVAYLI 30 mg/3 mL (10 mg/mL) vial and TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial are supplied as ready-to-use solution that do not need dilution prior to administration. Do not combine TECVAYLI vials of different concentrations to achieve treatment dose. Use aseptic technique to prepare and administer TECVAYLI. Preparation of TECVAYLI Refer to the following reference tables for the preparation of TECVAYLI. Refer to Tables 7, 8, and 9 below to determine the dosage based on predetermined weight ranges. Use Table 7 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 1 using TECVAYLI 30 mg/3 mL (10 mg/mL) vial. Table 7: Step-up Dose 1 (0.06 mg/kg) Injection Volumes using TECVAYLI 30 mg/3 mL (10 mg/mL) Vial Patient Body Weight (kg) Total Dose (mg) Volume of Injection (mL) Number of Vials (1 vial=3 mL) 35 to 39 2.2 0.22 1 40 to 44 2.5 0.25 1 45 to 49 2.8 0.28 1 50 to 59 3.3 0.33 1 60 to 69 3.9 0.39 1 70 to 79 4.5 0.45 1 80 to 89 5.1 0.51 1 90 to 99 5.7 0.57 1 100 to 109 6.3 0.63 1 110 to 119 6.9 0.69 1 120 to 129 7.5 0.75 1 130 to 139 8.1 0.81 1 140 to 149 8.7 0.87 1 150 to 160 9.3 0.93 1 Use Table 8 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 2 using TECVAYLI 30 mg/3 mL (10 mg/mL) vial. Table 8: Step-up Dose 2 (0.3 mg/kg) Injection Volumes using TECVAYLI 30 mg/3 mL (10 mg/mL) Vial Patient Body Weight (kg) Total Dose (mg) Volume of Injection (mL) Number of Vials (1 vial=3 mL) 35 to 39 11 1.1 1 40 to 44 13 1.3 1 45 to 49 14 1.4 1 50 to 59 16 1.6 1 60 to 69 19 1.9 1 70 to 79 22 2.2 1 80 to 89 25 2.5 1 90 to 99 28 2.8 1 100 to 109 31 3.1 2 110 to 119 34 3.4 2 120 to 129 37 3.7 2 130 to 139 40 4 2 140 to 149 43 4.3 2 150 to 160 47 4.7 2 Use Table 9 to determine total dose, injection volume and number of vials required based on patient's actual body weight for the treatment dose using TECVAYLI 153 mg/1.7 mL (90 mg/mL) vial. Table 9: Treatment Dose (1.5 mg/kg) Injection Volumes using TECVAYLI 153 mg/1.7 mL (90 mg/mL) Vial Patient Body Weight (kg) Total Dose (mg) Volume of Injection (mL) Number of Vials (1 vial=1.7 mL) 35 to 39 56 0.62 1 40 to 44 63 0.7 1 45 to 49 70 0.78 1 50 to 59 82 0.91 1 60 to 69 99 1.1 1 70 to 79 108 1.2 1 80 to 89 126 1.4 1 90 to 99 144 1.6 1 100 to 109 153 1.7 1 110 to 119 171 1.9 2 120 to 129 189 2.1 2 130 to 139 198 2.2 2 140 to 149 216 2.4 2 150 to 160 234 2.6 2 Remove the appropriate strength TECVAYLI vial from refrigerated storage [2 °C to 8 °C (36 °F to 46 °F)]. Once removed from refrigerated storage, equilibrate TECVAYLI to ambient temperature [15 °C to 30 °C (59 °F to 86 °F)] for at least 15 minutes. Do not warm TECVAYLI in any other way. Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake. Withdraw the required injection volume of TECVAYLI from the vial(s) into an appropriately sized syringe using a transfer needle. Each injection volume should not exceed 2 mL. Divide doses requiring greater than 2 mL equally into multiple syringes. TECVAYLI is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material. Replace the transfer needle with an appropriately sized needle for injection. Administration of TECVAYLI Inject the required volume of TECVAYLI into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, TECVAYLI may be injected into the subcutaneous tissue at other sites (e.g., thigh). If multiple injections are required, TECVAYLI injections should be at least 2 cm apart. Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact. Any unused product or waste material should be disposed in accordance with local requirements. Storage If the prepared dosing syringe(s) of TECVAYLI is not used immediately, store syringe(s) at 2 °C to 8 °C (36 °F to 46 °F) or at ambient temperature 15 °C to 30 °C (59 °F to 86 °F) for a maximum of 20 hours. Discard syringe(s) after 20 hours, if not used. Monitoring Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule [see Dosage and Administration (2.1) and Warnings and Precautions (5.1 , 5.2) ] .

None. None. ( 4 )

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%) are pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) 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 MajesTEC-1 The safety of TECVAYLI was evaluated in MajesTEC-1 [see Clinical Studies (14) ] which included adult patients with relapsed or refractory multiple myeloma. Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg, subcutaneously once weekly (N=165). Among patients who received TECVAYLI, 47% were exposed for 6 months or longer and 7% were exposed for one year or longer. The median age of patients who received TECVAYLI was 64 years (range: 33 to 84 years); 58% were male; 81% were White, 13% were Black or African American, and 2% were Asian. Serious adverse reactions occurred in 54% of patients who received TECVAYLI. Serious adverse reactions in >2% of patients included pneumonia (15%), cytokine release syndrome (8%), sepsis (6%), general physical health deterioration (6%), COVID-19 (6%), acute kidney injury (4.8%), pyrexia (4.8%), musculoskeletal pain (2.4%), and encephalopathy (2.4%). Fatal adverse reactions occurred in 5% of patients who received TECVAYLI, including COVID-19 (1.8%), pneumonia (1.8%), septic shock (0.6%), acute renal failure (0.6%), and hemoperitoneum (0.6%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 1.2% of patients. Adverse reactions resulting in permanent discontinuation of TECVAYLI included pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia. Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 73% of patients. Adverse reactions which required dosage interruption in >5% of patients included neutropenia, pneumonia, pyrexia, cytokine release syndrome, upper respiratory tract infection, and COVID-19. The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. Table 10 summarizes the adverse reactions in MajesTEC-1. Table 10: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received TECVAYLI in MajesTEC-1 Adverse Reactions TECVAYLI (N=165) Any Grade (%) Grade 3 or 4 (%) Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria. General disorders and administration site conditions Pyrexia 76 3 Only grade 3 adverse reactions occurred. Injection site reaction Injection site reaction includes application site erythema, injection site bruising, injection site cellulitis, injection site discomfort, injection site erythema, injection site hematoma, injection site induration, injection site inflammation, injection site edema, injection site pruritus, injection site rash, injection site reaction and injection site swelling. 37 0.6 Fatigue Fatigue includes asthenia and fatigue. 33 2.4 Chills 16 0 Pain Pain includes ear pain, flank pain, groin pain, oropharyngeal pain, pain, pain in jaw, toothache and tumor pain. 15 1.8 Edema Edema includes face edema, fluid overload, fluid retention, edema peripheral and peripheral swelling. 13 0 Immune system disorders Cytokine release syndrome 72 0.6 Hypogammaglobulinemia Hypogammaglobulinemia includes hypogammaglobulinemia and hypoglobulinemia. 11 1.2 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes arthralgia, back pain, muscle discomfort, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain and pain in extremity. 44 4.2 Bone pain 16 3 Infections Upper respiratory tract infection Upper respiratory tract infection includes bronchitis, influenza like illness, nasopharyngitis, pharyngitis, respiratory tract infection, respiratory tract infection bacterial, rhinitis, rhinovirus infection, sinusitis, tracheitis, upper respiratory tract infection and viral upper respiratory tract infection. 26 2.4 Pneumonia Pneumonia includes COVID-19 pneumonia, enterobacter pneumonia, lower respiratory tract infection, metapneumovirus pneumonia, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia klebsiella, pneumonia moraxella, pneumonia pneumococcal, pneumonia pseudomonal, pneumonia respiratory syncytial viral, pneumonia staphylococcal and pneumonia viral. Includes the following fatal adverse reactions: hemorrhage (n=1), pneumonia (n=3). 24 15 Urinary tract infection Urinary tract infection includes cystitis, cystitis escherichia, cystitis klebsiella, escherichia urinary tract infection, urinary tract infection and urinary tract infection bacterial. 11 5 Gastrointestinal disorders Nausea 25 0.6 Diarrhea 21 2.4 Constipation 18 0 Vomiting 12 0.6 Nervous system disorders Headache 25 0.6 Motor dysfunction Motor dysfunction includes cogwheel rigidity, dysgraphia, dysphonia, gait disturbance, hypokinesia, muscle rigidity, muscle spasms, muscular weakness, peroneal nerve palsy, psychomotor hyperactivity, tremor and VI th nerve paralysis. 16 0 Sensory neuropathy Sensory neuropathy includes dysesthesia, hypoesthesia, hypoesthesia oral, neuralgia, paresthesia, paresthesia oral, peripheral sensory neuropathy, sciatica and vestibular neuronitis. 15 1.2 Encephalopathy Encephalopathy includes agitation, apathy, aphasia, confusional state, delirium, depressed level of consciousness, disorientation, dyscalculia, hallucination, lethargy, memory impairment, mental status changes and somnolence. 13 0 Vascular disorders Hypotension 18 1.2 Hemorrhage Hemorrhage includes conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemoperitoneum, hemorrhoidal hemorrhage, lower gastrointestinal hemorrhage, melena, mouth hemorrhage and subdural hematoma. 12 1.8 Hypertension Hypertension includes essential hypertension and hypertension. 12 4.8 Respiratory, thoracic, and mediastinal disorders Hypoxia 18 1.8 Cough Cough includes allergic cough, cough, productive cough and upper-airway cough syndrome. 15 0 Cardiac disorders Cardiac arrhythmia Cardiac arrhythmia includes atrial flutter, cardiac arrest, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, tachycardia and ventricular tachycardia. 16 1.8 Metabolism and nutrition disorders Decreased appetite 11 0.6 Renal and urinary disorders Acute kidney injury Acute kidney injury includes acute kidney injury and renal impairment. 11 3.6 Clinically relevant adverse reactions in <10% of patients who received TECVAYLI included febrile neutropenia, sepsis, ICANS, seizure, Guillain-Barré syndrome, hepatic failure, and new onset or reactivated viral infections (including adenovirus, hepatitis B virus (HBV), cytomegalovirus (CMV), varicella zoster virus (VZV), herpes simplex virus (HSV), and progressive multifocal leukoencephalopathy (PML). Table 11 summarizes laboratory abnormalities in MajesTEC-1. Table 11: Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Multiple Myeloma Who Received TECVAYLI in MajesTEC-1 Laboratory Abnormality TECVAYLI (N=165 The denominator used to calculate the rate varied from 164 to 165 based on the number of patients with a baseline value and at least one post-treatment value. ) All Grades (%) Grade 3 or 4 (%) Laboratory toxicity grades are derived based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03. Hematology Lymphocyte count decreased 92 84 White blood cell decreased 86 41 Neutrophil count decreased 84 56 Platelet count decreased 71 22 Hemoglobin decreased 67 33 Chemistry Albumin decreased 68 6 Alkaline phosphatase increased 42 2.4 Phosphorus decreased 38 13 Gamma-glutamyl transferase increased 37 8 Sodium decreased 35 10 Aspartate aminotransferase increased 34 1.2 Calcium (corrected) decreased 31 1.2 Creatinine increased 30 3

TECVAYLI causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates. The highest risk of drug-drug interaction is expected to occur from 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 or concentrations of drugs that are CYP substrates where minimal concentration changes may lead to serious adverse reactions. Adjust the dose of the concomitant CYP substrate drug as needed.

Store refrigerated at 2 °C to 8 °C (36 °F to 46 °F) in the original carton to protect from light. Do not freeze.