Obecabtagene autoleucel

Dose For autologous use only. For intravenous use only. Strictly follow Administration instructions to minimize dosing errors [see Overdosage ] . 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. [See table below.] 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 and Dosage Forms and Strengths ] .

Administration AUCATZYL is for autologous use only. The patient's identity must match the patient identifiers on the AUCATZYL infusion bag. Do not infuse AUCATZYL if the information on the patient-specific label does not match the intended patient. Preparing the Patient for AUCATZYL Infusion Bone marrow assessment A bone marrow assessment must be available from a sample obtained within 7 days prior to the commencement of the lymphodepleting chemotherapy treatment, see Figure 1 .

Figure 1: AUCATZYL Treatment Schedule The bone marrow assessment will be used to determine the AUCATZYL dosage regimen based on a Bone Marrow Blast of > 20% or ≤ 20%, see Figure 3 . If the bone marrow assessment results are inconclusive: – Repeat biopsy or aspirate, NOTE a repeat biopsy or aspirate is only possible if lymphodepleting chemotherapy treatment has not started. – If results remain inconclusive, proceed with the Bone Marrow Blast of > 20% (i.e., administration of the 10 × 10 6 dose on Day 1) per the AUCATZYL Dose Schedule Planner.

An image of the treatment schedule. A bone marrow assessment will be performed 7-13 days prior to administration of Dose 1 of AUCATZYL. Following the bone marrow assessment, six days prior to administration of Dose 1 of AUCATZYL, fludarabine will be administered for four days and cyclophosphamide will be administered for two days starting with the first dose of fludarabine.

Dose 1 of AUCATZYL will be administered three days after lymphodepleting chemotherapy treatment (Day 1) and Dose 2 of AUCATZYL will be administered 8-12 days after administration of Dose 1. Pretreatment Confirm availability of AUCATZYL prior to starting the lymphodepleting chemotherapy treatment. Administer the lymphodepleting chemotherapy regimen before infusion of AUCATZYL: fludarabine (FLU) 30 mg/m 2 /day intravenously (IV) for four days and cyclophosphamide (CY) 500 mg/m 2 /day IV for two days starting with the first dose of fludarabine. (total dose: FLU 120 mg/m 2 ; CY 1000 mg/m 2 ), see Figure 1 .

Infuse AUCATZYL 3 days (± 1 day) after completion of lymphodepleting chemotherapy treatment (Day 1), allowing a minimum 48-hour washout. Delay AUCATZYL treatment if the patient is experiencing severe intercurrent infection. If the patient requires supplementary oxygen AUCATZYL should only be infused if considered appropriate based on the treating physician's benefit/risk assessment.

A delay to the second split dose may be required to manage toxicities [see Dosage Modification for Adverse Reactions and Warnings and Precautions ] . Premedication To minimize the risk of an infusion reaction, premedicate with acetaminophen approximately 30 minutes prior to AUCATZYL infusion. Avoid prophylactic use of systemic corticosteroids as they may interfere with the activity of AUCATZYL.

Receipt and storage of AUCATZYL AUCATZYL is supplied directly to the cellular therapy laboratory associated with the infusion center in the vapor phase of a liquid nitrogen shipper [see How Supplied/Storage and Handling ] . Confirm the patient's identity on the infusion bags with the patient identifiers on the shipper, see Figure 2 .

Figure 2: Patient Specific Identifiers Keep the infusion bag(s) in the metal cassette(s) and transfer AUCATZYL to the onsite controlled-access vapor phase of liquid nitrogen for storage below minus 150°C until ready for thaw and administration. Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds).

An image of an infusion bag highlighting the following patient specific identifiers: apheresis ID, chain of identity ID, patient hospital ID, patient name, and patient date of birth. Planning prior to AUCATZYL preparation The patient batch specific Release for Infusion certificate and Dose Schedule Planner will be provided in the shipper and via Autolus' Scheduling Portal.

Confirm the patient identifiers on the Release for Infusion certificate and infusion bags match, see Figure 2 . Ensure the patient's bone marrow assessment results are available. NOTE: The patient's bone marrow assessment results will be used to select the appropriate dosing regimen based on a Bone Marrow Blast of > 20% or ≤ 20%, see Figure 3 .

The AUCATZYL Dose Schedule Planner is provided with the Release for Infusion certificate and assists the determination of the appropriate dose regimen to be administered on Day 1 (3 days (± 1 day) after the completion of lymphodepleting chemotherapy) and Day 10 (± 2 days). Record the following information on the Dose Schedule Planner: The blast percentage from the patient's bone marrow assessment.

The AUCATZYL bag serial number(s); number of bag type required for each dose; and the specified volume to administer via syringe (for the 10 × 10 6 dose, Blue Bag) transcribed from the Release for Infusion certificate. The completion of the AUCATZYL Dose Schedule Planner will guide the treating physician on the number of bags required and preparation of AUCATZYL for the Day 1 and Day 10 (± 2 days) dose, see Figure 3 .

Dose Preparation Do NOT irradiate. Do NOT use a leukodepleting filter. Confirm the patient's identity with the patient identifiers on the Release for Infusion certificate. Contact Autolus Inc at 1-855-288-5227 if there are any discrepancies between the labels and the patient identifiers. Confirm tocilizumab and emergency equipment are available prior to infusion and during the recovery period.

Coordinate the timing of AUCATZYL thaw and infusion. Confirm the infusion time in advance and adjust the start time of AUCATZYL thaw such that it will be available for infusion when the patient is ready and will be infused within 60 minutes of thaw. Complete the AUCATZYL Dose Schedule Planner, as described above to identify the dose required for Day 1 and Day 10 (± 2 days) administration, see Figure 3 .

Follow the completed AUCATZYL Dose Schedule Planner and refer to the patient batch specific Release for Infusion certificate to verify the bag(s) required for Day 1 or Day 10 (± 2 days) dosing, see Figure 3 . Transfer and Thawing Using the completed Dose Schedule Planner for guidance, transfer ONLY the cassette(s)/ infusion bag(s) required for the given dosing day from the onsite vapor phase liquid nitrogen storage to an appropriate transfer vessel (i.e., a vapor phase liquid nitrogen shipper, maintaining a temperature below minus 150°C) for transport to the bag thaw location.

Transfer the required cassette(s) one by one, confirming the AUCATZYL bag serial numbers and patient identifiers on each infusion bag label, see Figure 2 . Time out of the vapor phase liquid nitrogen environment should be kept to an absolute minimum to avoid premature product thaw (recommend not to exceed 90 seconds). If more than one infusion bag is required on a given dosing day, thaw each infusion bag one at a time; Do NOT remove subsequent bags from the vapor phase liquid nitrogen storage (below minus 150°C) until the infusion of the previous bag is complete.

AUCATZYL must be continuously monitored during thawing process. Leave the AUCATZYL infusion bag in its overwrap, thaw at 37°C using a water bath or dry thaw method until there are no visible frozen clumps left in the infusion bag. Each bag should be gently massaged until the cells have just thawed. Thawing of each infusion bag takes between 2 and 8 minutes.

Remove from water bath or thaw device immediately after thawing is complete. Carefully remove the infusion bag from the overwrap taking care to avoid damage to the bag and ports. Gently mix the contents of the bag to disperse clumps of cellular material and administer immediately to the patient. Do not re-freeze or refrigerate thawed product.

Figure 3: AUCATZYL Dosage and Schedule [See table below.] The 100 × 10 6 (Orange Bag) and 300 × 10 6 (Red Bag) doses will be suspended in one or more infusion bags. and 300 × 10 6 Dose administered via bag infusion Bone Marrow Blast ≤ 20% Day 1 Day 10 (± 2 days) 100 × 10 6 Dose administered via bag infusion 10 × 10 6 Dose administered via syringe and 300 × 10 6 Dose administered via bag infusion Image

Infusion Instructions AUCATZYL is for autologous and intravenous use only. The patient's identity must match the patient identifiers on the Release for Infusion certificate and infusion bag. Contact Autolus Inc at 1-855-288-5227 if there are any discrepancies between the labels and the patient identifiers. Dose administration for 10 × 10 6 CD19 CAR-positive viable T cell Dose (Blue Bag) Withdrawal of the 10 × 10 6 dose into the syringe should be carried as follows: Prepare and administer AUCATZYL using aseptic technique.

Gently mix the contents of the bag to disperse clumps of cellular material. The volume to be administered for the 10 × 10 6 dose (Blue Bag) is specified on the Release for Infusion certificate. Use the smallest Luer-lock tip syringe necessary (1, 3, 5, or 10 mL) with a Luer-lock bag spike to draw up the volume as specified on the Release for Infusion certificate.

Do NOT use a leukodepleting filter. Do NOT use the syringe to mix the cells, see Figure 4 . Figure 4 : Syringe Infusion Guidance for the 10 × 10 6 Dose (Blue Bag) Withdraw the volume from the 10 × 10 6 Dose (Blue Bag) specified on the Release for Infusion certificate using a syringe fitted with a bag spike. Do not use the syringe to mix the cells Confirm withdrawal of the exact volume specified on the Release for Infusion certificate for the 10 × 10 6 Dose (Blue Bag).

Prime the tubing with normal saline prior to infusion. Once AUCATZYL has been drawn into the syringe, verify the volume and administer as an intravenous infusion as soon as possible as a slow push (approximately 0.5 mL/minute) through a central venous line (or large peripheral venous access line appropriate for blood products).

Complete infusion at room temperature within 60 minutes post thaw and flush the tubing line with 60 mL of normal saline. Dispose of any unused portion of AUCATZYL (according to local biosafety guidelines). An image depicting how to withdraw the dose from the bag. An image depicting that the syringe should not be used to mix.

An image depicting that only the volume specified in the release for infusion certificate should be withdrawn. Dose administration for 100 × 10 6 (Orange Bag) and/or 300 × 10 6 (Red Bag) CD19 CAR-positive viable T cells Refer to the Release for Infusion certificate and Dose Schedule Planner for the following details: The volume and total CD19 CAR-positive viable T cell number contained in each infusion bag.

The dose to be administered on the given dosing day and the number of bags required to deliver the specified CD19 CAR-positive viable T cell dose. If more than one bag is needed, thaw subsequent bags after the previous bag is fully administered. Prime the tubing with normal saline prior to infusion. Administer AUCATZYL via a gravity or peristaltic pump assisted IV infusion through a central venous line (or large peripheral venous access line appropriate for blood products).

Do NOT use a leukodepleting filter. Aseptic techniques must be applied when performing a venepuncture, spiking the ports, and through the cell administration process. Gently mix the contents of the bag during AUCATZYL infusion to disperse cell clumps. Infuse the entire content of the AUCATZYL infusion bag at room temperature within 60 minutes post thaw (infusion rate within 0.1 to 27 mL/minute).

After the entire content of the infusion bag is infused, rinse the bag with 30 mL of normal saline, then flush the tubing line with 60 mL of normal saline. Repeat steps 1 - 3 for any additional infusion bags required on the given dosing day. Do NOT initiate thaw of the next bag until infusion of the previous bag is complete.

AUCATZYL contains human blood cells that are genetically modified with replication-incompetent lentiviral vector. Follow universal precautions and local biosafety guidelines for handling and disposal of AUCATZYL to avoid potential transmission of infectious diseases. Monitoring Monitor patients for signs and symptoms of CRS, neurologic toxicities/ICANS and other acute toxicities daily for at least 7 days following each infusion.

Continue to monitor patients for at least 2 weeks following each infusion. Instruct patients to remain within proximity of a healthcare facility for at least 2 weeks following each infusion. Avoid driving for at least 2 weeks after each infusion.