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Brexucabtagene Autoleucel

FDA Drug Information • Also known as: Tecartus

Brand Names
Tecartus
Route
INTRAVENOUS
Dosage Form
SUSPENSION
Product Type
CELLULAR THERAPY

⚠ Boxed Warning (Black Box)

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving TECARTUS. Do not administer TECARTUS to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.1) ] . Neurologic toxicities, including life-threatening reactions, occurred in patients receiving TECARTUS, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with TECARTUS. Provide supportive care and/or corticosteroids, as needed [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.2) ] . T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies [see Warnings and Precautions (5.8) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving TECARTUS. Do not administer TECARTUS to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids ( 2.2 , 2.3 , 5.1 ). Neurologic toxicities, including life-threatening reactions, occurred in patients receiving TECARTUS, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with TECARTUS. Provide supportive care and/or corticosteroids, as needed ( 2.2 , 2.3 , 5.2 ). T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies ( 5.8 ).

Description

11 DESCRIPTION TECARTUS (brexucabtagene autoleucel) is a CD19-directed genetically modified autologous T cell immunotherapy. To prepare TECARTUS, a patient's own T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single-chain variable fragment (scFv) linked to CD28 and CD3-zeta co-stimulatory domains. The anti-CD19 CAR T cells are expanded and infused back into the patient, where they can recognize and eliminate CD19-expressing target cells. TECARTUS is prepared from the patient's peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells and activated with anti-CD3 and anti-CD28 antibodies in the presence of IL-2, then transduced with a replication-incompetent retroviral vector containing the anti-CD19 CAR transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and cryopreserved. The manufacture of TECARTUS includes a T cell enrichment step that may reduce the likelihood of circulating CD19-expressing tumor cells in patients' leukapheresis material driving the activation, expansion, and exhaustion of the anti-CD19 CAR T cells during the ex vivo manufacturing process. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-specific infusion bag. The product is thawed prior to infusion [see Dosage and Administration (2.2) , How Supplied/Storage and Handling (16) ] . In addition to T cells, TECARTUS may contain natural killer (NK) cells. The formulation contains CryoStor (dimethyl sulfoxide [DMSO], final concentration, 5%), sodium chloride (NaCl), and Human Serum Albumin (HSA).

What Is Brexucabtagene Autoleucel Used For?

1 INDICATIONS AND USAGE TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: TECARTUS is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL). This indication is approved under accelerated approval based on overall 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. Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). 1.1 Mantle Cell Lymphoma Adult patients with relapsed or refractory mantle cell lymphoma (MCL). This indication is approved under accelerated approval based on overall 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. 1.2 Acute Lymphoblastic Leukemia Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Each single infusion bag of TECARTUS contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. For autologous use only. For intravenous use only. Do NOT use a leukodepleting filter. Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of TECARTUS. ( 2.2 ) Verify the patient's identity prior to infusion. ( 2.2 ) Premedicate with acetaminophen and diphenhydramine. ( 2.2 ) Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.1 ) Dosing of TECARTUS is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. ( 2.1 ) MCL: dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells. ( 2.1 ) ALL: dose is 1 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 1 × 10 8 CAR-positive viable T cells. ( 2.1 ) 2.1 Dose Recommended Dosage for MCL The target dose is 2 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10 8 CAR-positive viable T cells. Recommended Dosage for ALL The target dose is 1 × 10 6 CAR-positive viable T cells per kg body weight, with a maximum of 1 × 10 8 CAR-positive viable T cells. 2.2 Administration TECARTUS is for autologous use only. The patient's identity must match the patient identifiers on the TECARTUS cassette and infusion bag. Do not infuse TECARTUS if the information on the patient-specific label does not match the intended patient. Preparing Patient for TECARTUS Infusion Confirm availability of TECARTUS prior to starting the lymphodepleting chemotherapy regimen. Pre-treatment MCL: Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m 2 intravenously and fludarabine 30 mg/m 2 intravenously on each of the fifth, fourth, and third day before infusion of TECARTUS. ALL: Administer a lymphodepleting chemotherapy regimen of fludarabine 25 mg/m 2 intravenously over 30 minutes on the fourth, third, and second day and administer cyclophosphamide 900 mg/m 2 over 60 minutes on the second day before infusion of TECARTUS. Premedication Premedicate with acetaminophen and diphenhydramine or another H1-antihistamine approximately 30 to 60 minutes prior to TECARTUS infusion. Avoid prophylactic use of systemic corticosteroids as it may interfere with the activity of TECARTUS. Preparation of TECARTUS for infusion Coordinate the timing of TECARTUS thaw and infusion. Confirm the infusion time in advance, and adjust the start time of TECARTUS thaw such that TECARTUS will be available for infusion when the patient is ready. Confirm patient identity: Prior to TECARTUS preparation, match the patient's identity with the patient identifiers on the TECARTUS cassette. Do not remove the TECARTUS infusion bag from the cassette if the patient information on the cassette label does not match the intended patient. Once patient identity is...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicities [see Warnings and Precautions (5.2) ] Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] Severe Infections [see Warnings and Precautions (5.5) ] Prolonged Cytopenias [see Warnings and Precautions (5.6) ] Hypogammaglobulinemia [see Warnings and Precautions (5.7) ] The most common non-laboratory adverse reactions (incidence greater than or equal to 20%) are: MCL: fever, CRS, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection with pathogen unspecified, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia. ( 6.1 ) ALL: fever, CRS, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Kite at 1-844-454-KITE (5483) 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. Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL) The safety of TECARTUS was evaluated in a Phase 2 single-arm clinical study (ZUMA-2) in which a total of 82 patients with relapsed/refractory MCL received a single dose of CAR-positive viable T cells (2 × 10 6 or 0.5 × 10 6 anti-CD19 CAR T cells/kg) that was weight-based [see Clinical Studies (14.1) ] . The most common adverse reactions (incidence ≥ 20%) were fever, CRS, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection with pathogen unspecified, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia. Serious adverse reactions occurred in 66% of patients. The most common serious adverse reactions (> 2%) were encephalopathy, fever, infection with pathogen unspecified, CRS, hypoxia, aphasia, renal insufficiency, pleural effusion, respiratory failure, bacterial infections, dyspnea, fatigue, arrhythmia, tachycardia, and viral infections. The most common (≥ 10%) Grade 3 or higher reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, fever, hyponatremia, hypertension, infection with pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia. Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with TECARTUS and Table 4 describes the laboratory abnormalities of Grade 3 or 4 that occurred in at least 10% of patients. Table 3. Summary of Adverse Reactions Observed in at Least 10% of Patients Treated with TECARTUS in ZUMA-2 (N=82) Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and Lymphatic System Disorders Coagulopathy Coagulopathy includes coagulopathy, disseminated intravascular coagulation, international normalized ratio increased. 10 2 Cardiac Disorders Tachycardias Tachycardias includes tachycardia, sinus tachycardia. 45 0 Bradycardias Bradycardias includes bradycardia, sinus bradycardia. 10 0 Non-ventricular Arrhythmias Non-ventricular arrhythmias includes atrial fibrillation, atrial flutter, cardiac flutter, palpitations, supraventricular tachycardia. 10 4 Gastrointestinal Disorders Nausea 35 1 Constipation 29 0 Diarrhea 28...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data with TECARTUS use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with TECARTUS to assess whether TECARTUS can cause fetal harm when administered to a pregnant woman. It is not known if TECARTUS has the potential to be transferred to the fetus. Based on the mechanism of action of TECARTUS, if the transduced cells cross the placenta, they may cause fetal toxicity, including B cell lymphocytopenia. Therefore, TECARTUS is not recommended for women who are pregnant. Pregnancy after TECARTUS infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% – 4% and 15% – 20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING TECARTUS is supplied in an infusion bag containing approximately 68 mL of frozen suspension of genetically modified autologous T cells in 5% DMSO and human serum albumin. Each TECARTUS infusion bag is individually packed in a metal cassette. TECARTUS is supplied in a liquid nitrogen dry shipper. Indication Infusion Bag NDC number Metal Cassette NDC number MCL 71287-219-01 71287-219-02 ALL 71287-220-01 71287-220-02 Match the identity of the patient with the patient identifiers on the cassette and infusion bag upon receipt. Store TECARTUS frozen in the vapor phase of liquid nitrogen (less than or equal to -150°C). TECARTUS may be stored for a single time at -80°C (+/- 10°C), for up to 90 days, and not exceeding the labeled expiration date. Do not return TECARTUS to storage in the vapor phase of liquid nitrogen after storage at -80°C. Thaw before using [see Dosage and Administration (2) ].

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.