Obecabtagene Autoleucel

FDA Drug Information • Also known as: Aucatzyl

Brand Names: Aucatzyl
Dosage Form: KIT
Product Type: CELLULAR THERAPY

⚠ Boxed Warning (Black Box)

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS) occurred in patients receiving AUCATZYL. Do not administer AUCATZYL to patients with active infection or inflammatory disorders. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.1) ]. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with AUCATZYL. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities. 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) occurred in patients receiving AUCATZYL. Do not administer AUCATZYL to patients with active infection or inflammatory disorders. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS. ( 2.2 , 2.3 , 5.1 ). Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including fatal or life-threatening reactions, occurred in patients receiving AUCATZYL, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with AUCATZYL. Prior to administering AUCATZYL, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities ( 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 AUCATZYL (obecabtagene autoleucel) is a CD19-directed genetically modified autologous Tcell immunotherapy comprised of the patient's T cells that are transduced with a lentiviral vector to express an anti-CD19 chimeric antigen receptor (CAR). The CAR is composed of a murine anti-CD19 single chain variable fragment (scFv) linked to 4-1BB and CD3-zeta co-stimulatory domains. AUCATZYL is prepared from the patient's own peripheral blood mononuclear cells, which are collected via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells, activated and transduced with a replication-incompetent lentiviral vector containing the CD19 CAR transgene. The transduced T cells are expanded in cell culture, washed, formulated into a suspension, and then cryopreserved. AUCATZYL is frozen in patient-specific infusion bag(s) and thawed prior to infusion [see Dosage and Administration (2.3) , How Supplied/Storage and Handling (16) ] . The product must pass a sterility test before it is released to the treatment center. The thawed product is a colorless to pale yellow, very opalescent suspension that is essentially free from visible foreign particles. In addition to T cells, AUCATZYL also contains non-transduced autologous T cells and non-T cells. The formulation contains phosphate-buffered saline (PBS) human serum albumin (HSA), ethylenediaminetetraacetic acid (EDTA) and 7.5% DMSO.

What Is Obecabtagene Autoleucel Used For?

1 INDICATION AND USAGE AUCATZYL is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). AUCATZYL is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) ( 1 ).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Do NOT use a leukodepleting filter ( 2.4 ). Prior to infusion Administer a lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide. ( 2.3 ). Ensure availability of bone marrow assessment results from a sample obtained within 7 days prior to start of lymphodepleting chemotherapy ( 2.3 ). Premedicate with acetaminophen ( 2.3 ). Confirm availability of tocilizumab prior to infusion ( 2.3 ). AUCATZYL Dose and Administration Verify patient's identity prior to infusion ( 2.3 ). Dosing is based on the Dose Schedule Planner ( 2.3 ). The total recommended dose of AUCATZYL is 410 × 10 6 CD19 chimeric antigen receptor (CAR)-positive viable T cells ( 2.1 ). The treatment regimen consists of a split dose infusion to be administered on Day 1 and Day 10 (± 2 days) ( 2.1 ). Dose to be administered is determined by the patient bone marrow blast assessment. See Full Prescribing Information for important preparation and administration information ( 2.3 , 2.4 ). 2.1 Dose For autologous use only. For intravenous use only. Strictly follow Administration instructions to minimize dosing errors [see Overdosage (10) ] . The total recommended dose of AUCATZYL is 410 × 10 6 CD19 chimeric antigen receptor (CAR)-positive viable T cells supplied in three to five infusion bags. Bags are supplied in three color-coded bag configurations (10 × 10 6 , 100 × 10 6 , 300 × 10 6 ) for split dose administration. Table 1: AUCATZYL Infusion Bag Configurations CAR-positive T Cell Dose (Bag Configuration) Color Code Volume Fully Infused 10 × 10 6 Blue 10 mL No (See Section 2.3 ) 100 × 10 6 Orange Variable Yes 300 × 10 6 Red Variable Yes The treatment regimen consists of a split dose infusion to be administered on Day 1 and Day 10 (± 2 days), see Figure 1 and Figure 3 . The dosage regimen will be determined by the tumor burden assessed by bone marrow blast percentage from a sample obtained within 7 days prior to the start of lymphodepletion [see Dosing and Administration (2.3 , 2.4) , Figure 1 and Figure 3 ] . See the Release for Infusion certificate and Dose Schedule Planner for the actual cell counts and volumes to be infused and to select the appropriate dosage regimen [see Dosage and Administration (2.4) and Dosage Forms and Strengths (3) ] . 2.2 Dosage Modification for Adverse Reactions Table 2: Dosage Modifications Intended to Reduce the Risk of Adverse Reactions Adverse Event Severity 1. Based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, and Grade 4 is life-threatening. Actions Second Split Dose Day 10 (± 2 days) Cytokine Release Syndrome following the first split dose [see Warnings and Precautions (5.1) ]. Grade 2 Consider postponing AUCATZYL infusion up to Day 21 to allow for the CRS to resolve to Grade ≤ 1. Grade ≥ 3 Discontinue treatment. Immune Effector Cell-associated Neurotoxicity Syndrome following the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common (non-laboratory) adverse reactions (incidence ≥ 20%) are: CRS, infections - pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Autolus Inc at toll-free phone 1-855-288-5227 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch ( 17 ). 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. The safety of AUCATZYL was evaluated in the FELIX study in which 100 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) received AUCATZYL at a median dose of 410 × 10 6 CD19 CAR-positive viable T cells (range: 10 to 480 × 10 6 CD19 CAR-positive viable T cells with 90% of patients receiving the recommended dose of 410 × 10 6 ± 25%) [see Clinical Studies (14) ] . The most common serious adverse reactions of any Grade (incidence ≥ 2%) included infections-pathogen unspecified, febrile neutropenia, ICANS, CRS, fever, bacterial infectious disorders, encephalopathy, fungal infections, hemorrhage, respiratory failure, hypotension, ascites, HLH/MAS, thrombosis and hypoxia. Nine patients (9%) experienced fatal adverse reactions which included infections (sepsis, pneumonia, peritonitis), ascites, pulmonary embolism, acute respiratory distress syndrome, HLH/MAS and ICANS. Of the 9 patients, five patients who died from infections had pre-existing and ongoing neutropenia prior to receiving bridging therapy, lymphodepletion chemotherapy treatment and/or AUCATZYL. Table 3 summarizes the adverse reactions (excluding laboratory abnormalities) that occurred in at least 10% of patients. Table 4 presents the most common Grade 3 or 4 laboratory abnormalities, occurring in at least 10% of patients. Table 3: Adverse Reactions Occurring in ≥ 10% of Patients in FELIX Study (N=100) Adverse Reaction Any Grade (%) Grade 3 or Higher (%) Blood and lymphatic system disorders Febrile neutropenia 26 26 Coagulopathy Is a composite that includes multiple related terms. 10 6 Cardiac disorders Tachycardia 12 0 Gastrointestinal disorders Nausea 29 2 Diarrhea 26 0 Vomiting 18 0 Abdominal pain 16 1 Constipation 11 0 General disorders and administration site conditions Fever 29 1 Pain 23 0 Fatigue 22 3 Edema 12 0 Chills 11 0 Immune system disorders Cytokine release syndrome 75 3 Hypogammaglobulinemia 10 2 Infections and infestations Infections - pathogen unspecified 44 31 Viral infections excluding COVID-19 16 1 COVID-19 18 6 Bacterial infections 26 11 Fungal infections 15 5 Investigations Weight decreased 11 2 Metabolism and nutrition disorders Decreased appetite 13 3 Musculoskeletal and connective tissue disorders Musculoskeletal pain 36 4 Nervous system disorders Immune effector cell-associated neurotoxicity syndrome 24 7 Headache 22 0 Encephalopathy Encephalopathy includes aphasia, cognitive disorder, confusional state, depressed level of consciousness, disturbance in attention, dysarthria, dysgraphia, encephalopathy, lethargy, memory impairment, mental status changes, posterior reversible encephalopathy syndrome, somnolence. 21 4 Dizziness 14 0 Respiratory, thoracic and mediastinal disorders Cough 14 0 Skin and subcutaneous tissue disorders Rash 17 1 Vascular disorders Hypotension 23 4 Hemorrhage 20 4 Other clinically important adverse reactions that occurred in less than 10% of patients treated with AUCATZYL include the following: Cardiac disorders: arrhythmia (5%), palpitations (2%), cardiac failure (1%). Endocrine disorders: adrenal insufficiency (2%). Eye disorders: visual impairment (2%). Gastrointestinal disorders: stomatitis (5%), ascites (4%). Immune system...

Contraindications

4 CONTRAINDICATIONS None. None ( 4 ).

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are limited available data with AUCATZYL use in pregnant women. In the FELIX study, one patient became pregnant 6 months following treatment with AUCATZYL. The patient had a premature delivery at 30 weeks of pregnancy. No animal reproductive and developmental toxicity studies have been conducted with AUCATZYL to assess whether AUCATZYL can cause fetal harm when administered to a pregnant woman. It is not known if AUCATZYL has the potential to be transferred to the fetus and cause fetal toxicity. Based on the mechanism of action of AUCATZYL, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobinemia. Therefore, AUCATZYL is not recommended for women who are pregnant. Pregnancy after AUCATZYL infusion should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Overdosage

10 OVERDOSAGE In FELIX study (all cohorts N=127), occurrences of overdose were observed at the administration of the first dose in 4% (5/127) of patients. All 5 patients had bone marrow blasts > 20% and should have received a first dose of 10 × 10 6 CAR-positive viable T cells but instead received a higher dose between 68 and 103 × 10 6 CAR-positive viable T cells. CRS, ICANS and HLH, including severe events, were observed in patients who received overdose of AUCATZYL. In the event of a suspected overdose, closely monitor patients for any adverse reactions and administer treatment according to institutional practice and treatment guidelines.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING AUCATZYL 410 × 10 6 CD19 CAR-positive viable T cells NDC (83047-410-04) is supplied in three to five infusion bags (see below) containing a frozen suspension of genetically modified autologous T cells in PBS, HSA, EDTA and 7.5% DMSO. Each infusion bag of AUCATZYL is individually packed within an overwrap and then enclosed within a metal cassette. AUCATZYL is shipped from the manufacturing facility to the cellular therapy laboratory associated with the infusion center in a cryogenic shipper charged with liquid nitrogen. A Release for Infusion certificate is provided to the infusion site in the shipper and via the Autolus Scheduling Portal with the product. Infusion bag configurations Color Code Fill Volume Range (min – max) NDC Number 10 × 10 6 CD19 CAR-positive viable T cells in one 50 mL infusion bag Blue 10 mL 83047-010-10 100 × 10 6 CD19 CAR-positive viable T cells in one or more 50 mL infusion bags Orange 10 to 20 mL 83047-100-10 100 × 10 6 CD19 CAR-positive viable T cells in one 250 mL infusion bag Orange 30 to 70 mL 83047-100-30 300 × 10 6 CD19 CAR-positive viable T cells in one or more 250 mL infusion bags Red 30 to 70 mL 83047-300-30 Match the identity of the patient with the patient identifiers on the infusion bag upon receipt [see Dosage and Administration (2.3) ] . Store AUCATZYL frozen in the vapor phase of liquid nitrogen (below minus 150°C) [see Dosage and Administration (Section 2.3) ] . Thaw AUCATZYL prior to infusion [see Dosage and Administration (2.3) ] . Do not re-freeze after thawing. Do not irradiate AUCATZYL, as this could lead to inactivation.

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.