Home › Drugs › Talquetamab

Talquetamab

FDA Drug Information • Also known as: Talvey

Brand Names
Talvey
Route
SUBCUTANEOUS
Dosage Form
INJECTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

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 TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.2 , 2.5 ) , Warnings and Precautions (5.1) ] . Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life threatening or fatal reactions, can occur with TALVEY. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY based on severity [see Dosage and Administration (2.5) , Warnings and Precautions (5.2) ] . Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.3) ] . 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 TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity. ( 2.2 , 2.5 , 5.1 ) Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur in patients receiving TALVEY. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold or permanently discontinue TALVEY based on severity. ( 2.5 , 5.2 ) TALVEY is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS). ( 5.3 )

Description

11 DESCRIPTION Talquetamab-tgvs is a bispecific GPRC5D-directed CD3 T-cell engager. It is a humanized IgG4 proline, alanine, alanine (IgG4-PAA)-based bispecific antibody produced by Chinese hamster ovary (CHO) cells using recombinant DNA technology. Talquetamab-tgvs consists of an anti-GPRC5D 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 talquetamab-tgvs is 147 kDa. TALVEY ® (talquetamab-tgvs) injection is a sterile, preservative-free colorless to light yellow solution supplied in a single-dose vial for subcutaneous administration. Each TALVEY 1.5 mL single-dose vial contains 3 mg of talquetamab-tgvs, edetate disodium (0.027 mg), glacial acetic acid (0.36 mg), polysorbate 20 (0.6 mg), sodium acetate (1.39 mg), sucrose (120 mg), and Water for Injection, USP. The pH is 5.2. Each TALVEY 1 mL single-dose vial contains 40 mg of talquetamab-tgvs, edetate disodium (0.018 mg), glacial acetic acid (0.24 mg), polysorbate 20 (0.4 mg), sodium acetate (0.90 mg), sucrose (80 mg), and Water for Injection, USP. The pH is 5.2.

What Is Talquetamab Used For?

1 INDICATIONS AND USAGE TALVEY 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 and durability of response [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). TALVEY is a bispecific GPRC5D-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 and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For subcutaneous injection. ( 2.2 ) Patients should be hospitalized for 48 hours after all doses within the step-up dosing schedule. ( 2.1 ) Administer pretreatment medications as recommended. ( 2.3 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.6 ) TALVEY Weekly Dosing Schedule ( 2.2 ) Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 First treatment dose 0.4 mg/kg Weekly dosing schedule One week after first treatment dose and weekly thereafter Maintain a minimum of 6 days between weekly doses. Subsequent treatment doses 0.4 mg/kg once weekly TALVEY Biweekly (Every 2 Weeks) Dosing Schedule ( 2.2 ) Dosing schedule Day Dose Based on actual body weight. Step-up dosing schedule Day 1 Step-up dose 1 0.01 mg/kg Day 4 Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions. Step-up dose 2 0.06 mg/kg Day 7 Step-up dose 3 0.4 mg/kg Day 10 Dose may be administered between 2 to 7 days after step-up dose 3. First treatment dose 0.8 mg/kg Biweekly (every 2 weeks) dosing schedule Two weeks after first treatment dose and every 2 weeks thereafter Maintain a minimum of 12 days between biweekly (every 2 weeks) doses. Subsequent treatment doses 0.8 mg/kg every 2 weeks 2.1 Important Dosing Information Administer TALVEY subcutaneously according to the step-up dosing schedule in Tables 1 and 2 to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration (2.2) ] . Administer pretreatment medications prior to each dose of TALVEY in the step-up dosing schedule as recommended [see Dosage and Administration (2.2 , 2.3) ]. TALVEY should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Warnings and Precautions (5.1 , 5.2) ] . 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 TALVEY step-up dosing schedule [see Dosage and Administration (2.5) and Warnings and Precautions (5.1 , 5.2) ] . 2.2 Recommended Dosage For subcutaneous injection. Administer pretreatment medications prior to each dose of TALVEY in the step-up dosing schedule [see Dosage and Administration (2.3) ] . Administer TALVEY subcutaneously on a weekly or biweekly (every 2 weeks) dosing schedule according to Table 1 or Table 2. Continue treatment until disease progression or unacceptable toxicity. Table 1: TALVEY Weekly Dosing Schedule Dosing...

Side Effects (Adverse Reactions)

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) ] Oral Toxicity and Weight Loss [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Cytopenias [see Warnings and Precautions (5.6) ] Skin Toxicity [see Warnings and Precautions (5.7) ] Hepatotoxicity [see Warnings and Precautions (5.8) ] The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. ( 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. 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 MonumenTAL-1 The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY followed by TALVEY 0.4 mg/kg subcutaneously weekly thereafter. Patients treated with the biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) followed by TALVEY 0.8 mg/kg subcutaneously every 2 weeks thereafter. The duration of exposure for the 0.4 mg/kg weekly regimen was 5.9 (range: 0.0 to 25.3) months (N=186) and for the 0.8 mg/kg biweekly (every 2 weeks) regimen, it was 3.7 (range: 0.0 to 17.9) months (N=153). Serious adverse reactions occurred in 47% of patients who received TALVEY. Serious adverse reactions in ≥ 2% of patients included CRS (13%), bacterial infection (8%) including sepsis, pyrexia (4.7%), ICANS (3.8%), COVID-19 (2.7%), neutropenia (2.1%), and upper respiratory tract infection (2.1%). Fatal adverse reactions occurred in 3.2% of patients who received TALVEY, including COVID - 19 (0.6%), dyspnea (0.6%), general physical health deterioration (0.6%), bacterial infection (0.3%) including sepsis, basilar artery occlusion (0.3%), fungal infection (0.3%), infection (0.3%), and pulmonary embolism (0.3%). Permanent discontinuation of TALVEY due to an adverse reaction occurred in 9% of patients. Adverse reactions which resulted in permanent discontinuation of TALVEY in > 1% of patients included ICANS. Dosage interruptions of TALVEY due to an adverse reaction occurred in 56% of patients. Adverse reactions which required dosage interruption in > 5% of patients included pyrexia (15%), CRS (12%), upper respiratory tract infection (9%), COVID-19 (9%), bacterial infection (7%) including sepsis, neutropenia (6%), and rash (6%). The most common adverse reactions (≥ 20%) were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥ 30%) were lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. Table 13 summarizes the adverse reactions in MonumenTAL-1. Table 13: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY N=339 System Organ Class Adverse Reaction Any...

Drug Interactions

7 DRUG INTERACTIONS For certain cytochrome P450 (CYP) substrates, minimal changes in the substrate concentration may lead to serious adverse reactions. Monitor for toxicity or drug concentrations of such CYP substrates when co-administered with TALVEY. Talquetamab-tgvs causes release of cytokines [see Clinical Pharmacology (12.2) ] that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. Increased exposure of CYP substrates is more likely to occur from initiation of the TALVEY step-up dosing schedule up to 14 days after the first treatment dose and during and after CRS [see Warnings and Precautions (5.1) ] .

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on the mechanism of action, TALVEY may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TALVEY in pregnant women to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with talquetamab-tgvs. Talquetamab-tgvs causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, TALVEY has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING TALVEY ® (talquetamab-tgvs) injection is a sterile, preservative-free, colorless to light yellow solution supplied as follows: One 3 mg/1.5 mL (2 mg/mL) single-dose vial in a carton: NDC: 57894-469-01 One 40 mg/mL single-dose vial in a carton: NDC: 57894-470-01 Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.