Drug Detail:Tecvayli (Teclistamab-cqyv)
Drug Class: Miscellaneous antineoplastics
Highlights of Prescribing Information
TECVAYLI ®(teclistamab-cqyv) injection, for subcutaneous use
Initial U.S. Approval: 2022
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
See full prescribing information for complete boxed warning.
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity. ( 2.1, 2.4, 5.1)
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity. ( 2.4, 5.2)
TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS). ( 5.3)
Indications and Usage for Tecvayli
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 confirmatory trial(s). ( 1)
Tecvayli Dosage and Administration
| Dosing Schedule | Day | Dose | |
|---|---|---|---|
| Step-up Dosing Schedule | Day 1 | Step-up dose 1 | 0.06 mg/kg |
| Day 4 | Step-up dose 2 | 0.3 mg/kg | |
| Day 7 | 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 |
- 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)
- See Full Prescribing Information for instructions on preparation and administration. ( 2.5)
Dosage Forms and Strengths
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)
Contraindications
None. ( 4)
Warnings and Precautions
- Hepatotoxicity: Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. ( 5.4)
- Infections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold in patients with active infection during the step-up dosing schedule. ( 2.4, 5.5)
- Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment. ( 5.6)
- Hypersensitivity and Other Administration Reactions: Systemic administration-related reactions and local injection site reactions can occur. Withhold or consider permanent discontinuation based on severity. ( 2.4, 5.7)
- Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.8, 8.1, 8.3)
Adverse Reactions/Side Effects
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-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Use In Specific Populations
Lactation: Advise not to breastfeed. ( 8.2)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 8/2023
Full Prescribing Information
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.1, 2.4)and Warnings and Precautions (5.1)] .
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur with TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity [see Dosage and Administration (2.4)and Warnings and Precautions (5.2)] .
Because of the risk of CRS and neurologic toxicity, including ICANS, TECVAYLI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TECVAYLI and TALVEY REMS [see Warnings and Precautions (5.3)] .
1. Indications and Usage for Tecvayli
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).
2. Tecvayli Dosage and Administration
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.
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)] .
| Dosing schedule | Day | Dose | |
|---|---|---|---|
|
|||
| Step-up dosing schedule * | Day 1 | Step-up dose 1 | 0.06 mg/kg |
| Day 4 † | Step-up dose 2 | 0.3 mg/kg | |
| Day 7 ‡ | 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 |
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)].
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)].
| Last dose administered | Duration of delay from 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). * |
| 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 † | Restart TECVAYLI step-up dosing schedule at step-up dose 1 (0.06 mg/kg). * | |
| Any treatment dose | 8 days to 28 days | Continue TECVAYLI weekly dosing schedule at treatment dose (1.5 mg/kg). |
| More than 28 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 5for recommended actions for adverse reactions of CRS, neurologic toxicity, and ICANS. See Table 6for 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.
| Grade * | Presenting Symptoms | Actions |
|---|---|---|
|
||
| Grade 1 | Temperature ≥100.4°F (38°C) † |
|
| 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 §or blow-by. |
|
| 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:
|
Recurrent Grade 3 CRS or Grade 3 CRS with Duration 48 Hours or Longer:
|
||
| 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). |
|
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.
| Adverse Reaction | Severity * | Actions |
|---|---|---|
|
||
| Neurologic Toxicity *(excluding ICANS) | Grade 1 |
|
| Grade 2
Grade 3 (First occurrence) |
|
|
| Grade 3 (Recurrent)
Grade 4 |
|
|
| Grade * | Presenting Symptoms † | Actions |
|---|---|---|
|
||
| Grade 1 | ICE score 7–9
‡,
or depressed level of consciousness §: awakens spontaneously. |
|
| Grade 2 | ICE score 3–6
‡,
or depressed level of consciousness §: awakens to voice. |
|
| Grade 3 | ICE score 0–2
‡,
or depressed level of consciousness §: awakens only to tactile stimulus, or seizures §, either:
| First Occurrence of Grade 3 ICANS:
|
Recurrent Grade 3 ICANS:
|
||
| Grade 4 | ICE score 0
‡,
or depressed level of consciousness §: either:
|
|
| Adverse Reactions | Severity | Actions |
|---|---|---|
|
||
| Infections *[see Warnings and Precautions (5.5)] | All Grades |
|
| Grade 3 |
|
|
| Grade 4 |
|
|
| Hematologic Toxicities [see Warnings and Precautions (5.6)and Adverse Reactions (6.1)] | Absolute neutrophil count less than 0.5 × 10 9/L |
|
| Febrile neutropenia |
|
|
| Hemoglobin less than 8 g/dL |
|
|
| Platelet count less than 25,000/mcL
Platelet count between 25,000/mcL and 50,000/mcL with bleeding |
|
|
| Other Non-Hematologic Adverse Reactions
*
[see Warnings and Precautions (5.4)and Adverse Reactions (6.1)] | Grade 3 |
|
| Grade 4 |
|
|
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.
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.
| 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.
| 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.
| 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°Fto 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.
5. Warnings and Precautions
5.1 Cytokine Release Syndrome
TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions [see Adverse Reactions (6.1)] .
In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days.
Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).
Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.1, 2.4)] . Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly [see Dosage and Administration (2.2, 2.4)] .
At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity [see Dosage and Administration (2.4)] .
TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].
5.2 Neurologic Toxicity including ICANS
TECVAYLI can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) [see Adverse Reactions (6.1)] .
In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%).
With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI.
In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose [see Adverse Reactions (6.1)] . Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines [see Dosage and Administration (2.4)] .
Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness [see Adverse Reactions (6.1)] . Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves [see Dosage and Administration (2.1)] .
TECVAYLI is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)].
5.3 TECVAYLI and TALVEY REMS
TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)].
Notable requirements of the TECVAYLI and TALVEY REMS include the following:
- Prescribers must be certified with the program by enrolling and completing training.
- Prescribers must counsel patients receiving TECVAYLI about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with Patient Wallet Card.
- Pharmacies and healthcare settings that dispense TECVAYLI must be certified with the TECVAYLI and TALVEY REMS program and must verify prescribers are certified through the TECVAYLI and TALVEY REMS program.
- Wholesalers and distributers must only distribute TECVAYLI to certified pharmacies or healthcare settings.
Further information about the TECVAYLI and TALVEY REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.
5.4 Hepatotoxicity
TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.4)].
5.5 Infections
TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2% [see Adverse Reactions (6.1)] .
Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines [see Dosage and Administration (2.2)] .
Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity [see Dosage and Administration (2.4)] .
Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis [see Dosage and Administration (2.2)] .
5.6 Neutropenia
TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients [see Adverse Reactions (6.1)].
Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines.
Monitor patients with neutropenia for signs of infection.
Withhold TECVAYLI based on severity [see Dosage and Administration (2.4)] .
5.7 Hypersensitivity and Other Administration Reactions
TECVAYLI can cause both systemic administration-related reactions and local injection-site reactions.
5.8 Embryo-Fetal Toxicity
Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose [see Use in Specific Populations (8.1, 8.3)] .
6. Adverse Reactions/Side Effects
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)]
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.
| 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 * |
| Injection site reaction † | 37 | 0.6 * |
| Fatigue ‡ | 33 | 2.4 * |
| Chills | 16 | 0 |
| Pain § | 15 | 1.8 * |
| Edema ¶ | 13 | 0 |
| Immune system disorders | ||
| Cytokine release syndrome | 72 | 0.6 * |
| Hypogammaglobulinemia # | 11 | 1.2 * |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain Þ | 44 | 4.2 * |
| Bone pain | 16 | 3 * |
| Infections | ||
| Upper respiratory tract infection ß | 26 | 2.4 * |
| Pneumonia àè | 24 | 15 |
| Urinary tract infection ð | 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 ø | 16 | 0 |
| Sensory neuropathy ý | 15 | 1.2 * |
| Encephalopathy £ | 13 | 0 |
| Vascular disorders | ||
| Hypotension | 18 | 1.2 * |
| Hemorrhage ¥è | 12 | 1.8 |
| Hypertension Π| 12 | 4.8 * |
| Respiratory, thoracic, and mediastinal disorders | ||
| Hypoxia | 18 | 1.8 |
| Cough œ | 15 | 0 |
| Cardiac disorders | ||
| Cardiac arrhythmia Ɖ | 16 | 1.8 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 11 | 0.6 * |
| Renal and urinary disorders | ||
| Acute kidney injury A | 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), and herpes simplex virus (HSV)).
Table 11 summarizes laboratory abnormalities in MajesTEC-1.
| Laboratory Abnormality | TECVAYLI
(N=165 *) |
|
|---|---|---|
| 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. | ||
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| 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 |
7. Drug Interactions
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.
8. Use In Specific Populations
8.3 Females and Males of Reproductive Potential
TECVAYLI may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] .
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. There is an insufficient number of patients 75 years of age or older to assess whether there are differences in safety or effectiveness.
11. Tecvayli 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.
12. Tecvayli - Clinical Pharmacology
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.
12.2 Pharmacodynamics
Serum concentrations of cytokines (IL-6, IL-10, TNF-α, and IFN-γ) and IL-2R were measured before and after administration of step-up dose 1, step-up dose 2, and the first three treatment doses of TECVAYLI. Increased concentrations of IL-6, IL-10, and IL-2R were observed during this period.
12.3 Pharmacokinetics
The C maxand AUC tauof teclistamab-cqyv after the first subcutaneous treatment dose increase proportionally over a dosage range of 0.08 mg/kg to 3 mg/kg (0.05 to 2 times the approved recommended treatment dosage). Ninety percent of steady state exposure was achieved after 12 weekly treatment doses. The mean accumulation ratio between the first and 13 thweekly treatment dose of teclistamab-cqyv 1.5 mg/kg was 4.2-fold for C max, 4.1-fold for C trough, and 5.3-fold for AUC tau.
The C max, C trough, and AUC tauof teclistamab-cqyv are presented in Table 12.
| Pharmacokinetic Parameter | Teclistamab-cqyv
Geometric Mean (CV%) |
|---|---|
| SD = standard deviation; C max= Maximum serum teclistamab-cqyv concentration; C trough= Serum teclistamab-cqyv concentration prior to next dose; CV = geometric coefficient of variation; AUC tau= Area under the concentration-time curve over the weekly dosing interval. | |
|
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| C max(mcg/mL) | 23.8 (55%) |
| C trough(mcg/mL) | 21.1 (63%) |
| AUC tau(mcg∙h/mL) | 3,838 (57%) |
12.6 Immunogenicity
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of teclistamab-cqyv or of other teclistamab products.
During treatment in MajesTEC-1 (up to 27 months), 1/186 (0.5%) of patients treated with subcutaneous TECVAYLI at various dosages developed anti-teclistamab-cqyv antibodies. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of teclistamab products is unknown.
14. Clinical Studies
The efficacy of TECVAYLI was evaluated in patients with relapsed or refractory multiple myeloma in a single-arm, open-label, multi-center study (MajesTEC-1, NCT03145181 [Phase 1] and NCT04557098 [Phase 2]). The study included patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The study excluded patients who had stroke, seizure, allogeneic stem cell transplantation within the past 6 months, Eastern Cooperative Oncology Group (ECOG) performance score of 2 or higher, known active CNS involvement or clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease, with the exception of vitiligo, Type 1 diabetes, and prior autoimmune thyroiditis.
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 thereafter until disease progression or unacceptable toxicity [see Dosage and Administration (2.1)] .
The efficacy population included 110 patients. The median age was 66 (range: 33 to 82) years with 16% of patients 75 years of age or older; 56% were male; 91% were White, 5% were Black or African American, 3% were Asian. The International Staging System (ISS) at study entry was Stage I in 50%, Stage II in 38%, and Stage III in 12% of patients. High-risk cytogenetics (presence of del(17p), t(4;14) and t(14;16)) were present in 25% of patients. Seventeen percent of patients had extramedullary plasmacytomas. Patients with prior BCMA-targeted therapy were not included in the efficacy population.
The median number of prior lines of therapy was 5 (range: 2 to 14); 78% of patients had received at least 4 prior lines of therapy. Eighty-one percent of patients received prior stem cell transplantation. All patients had received prior therapy with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and 76% were triple-class refractory (refractory to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody).
Efficacy was established based on overall response rate (ORR) as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria (see Table 13).
The median time to first response was 1.2 months (range: 0.2 to 5.5 months). With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6% (95% CI: 80.3%, 95.7%) at 6 months and 66.5% (95% CI: 38.8%, 83.9%) at 9 months.
| N=110 | |
|---|---|
| NE=not estimable | |
|
|
| Overall response rate (ORR: sCR+CR+VGPR+PR) n(%) | 68 (61.8) |
| 95% CI (%) | (52.1, 70.9) |
| Complete response (CR) or better * | 31 (28.2) |
| Very good partial response (VGPR) | 32 (29.1) |
| Partial response (PR) | 5 (4.5) |
| Duration of Response (DOR) (months) | |
| DOR (Months): Median (95% CI) | NE (9.0, NE) |
16. How is Tecvayli supplied
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
17. Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
| MEDICATION GUIDE
TECVAYLI ®[tek vay' lee] (teclistamab-cqyv) injection, for subcutaneous use |
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|---|---|---|---|---|
| This Medication Guide has been approved by the U.S. Food and Drug Administration. | Revised: August 2023 | |||
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What is the most important information I should know about TECVAYLI? TECVAYLI may cause side effects that are serious, life-threatening or lead to death, including Cytokine Release Syndrome (CRS) and Neurologic problems. Call your healthcare provider right away if you develop any of the signs or symptoms of CRS or neurologic problems listed below at any time during your treatment with TECVAYLI: Cytokine Release Syndrome (CRS). Signs and symptoms of CRS may include: |
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| Neurologic problems. Symptoms of neurologic problems with TECVAYLI include: | ||||
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You will receive a Patient Wallet Card from your healthcare provider. Carry the Patient Wallet Card with you at all times and show it to all of your healthcare providers.The Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the Patient Wallet Card.You may need to be treated in a hospital.
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| What is TECVAYLI?
TECVAYLI is a prescription medicine to treat adults with multiple myeloma who:
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Before you receive TECVAYLI, tell your healthcare provider about all of your medical conditions, including if you:
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How will I receive TECVAYLI?
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What are the possible side effects of TECVAYLI?
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The most common side effects of TECVAYLI include: |
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| The most common severe abnormal lab test results with TECVAYLI include: decreased white blood cells, red blood cells and platelets.
These are not all the possible side effects of TECVAYLI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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| General Information about TECVAYLI.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider for information about TECVAYLI that is written for health professionals. |
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| What are the ingredients of TECVAYLI?
Active ingredient: teclistamab-cqyv Inactive ingredients: edetate disodium, glacial acetic acid, polysorbate 20, sodium acetate, sucrose, Water for Injection Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044, USA U.S. License Number 1864 © 2022 Janssen Pharmaceutical Companies For patent information: www.janssenpatents.com For more information about TECVAYLI go to www.TECVAYLI.com or call 1-800-526-7736. |
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| TECVAYLI
teclistamab injection |
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teclistamab injection |
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| Labeler - Janssen Biotech, Inc. (099091753) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Janssen Biotech, Inc. | 038978363 | api manufacture(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Biogen MA, Inc. | 841087823 | api manufacture(57894-449, 57894-450) , analysis(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Janssen Sciences Ireland Unlimited Company | 986030167 | api manufacture(57894-449, 57894-450) , analysis(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Janssen Biologics B.V. | 409612918 | api manufacture(57894-449, 57894-450) , analysis(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| BioReliance Corporation | 147227730 | analysis(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Patheon Manufacturing Services LLC | 079415560 | analysis(57894-449, 57894-450) , manufacture(57894-449, 57894-450) , label(57894-449, 57894-450) , pack(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| AndersonBrecon, Inc. | 053217022 | pack(57894-449, 57894-450) , label(57894-449, 57894-450) | |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
|---|---|---|---|
| Cilag AG | 483237103 | analysis(57894-449, 57894-450) | |
