Glofitamab

Important Dosing Information Administer only as an intravenous infusion through a dedicated infusion line that includes a sterile 0.2-micron in-line filter. Administer COLUMVI diluted solution via intravenous bag infusion. The 2.5 mg dose may alternatively be administered via intravenous syringe infusion [see Dosage and Administration (2.5 , 2.6 , 2.7 )] .

COLUMVI should only be administered by a healthcare professional with immediate access to appropriate medical support, including supportive medications to manage severe CRS [see Dosage and Administration ] . Ensure adequate hydration before administering COLUMVI. Premedicate before each dose [see Dosage and Administration ] .

Following pretreatment with obinutuzumab, administer COLUMVI according to the step-up dosing schedule in Table 1 with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS [see Dosage and Administration ] . Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8) [see Dosage and Administration and Warnings and Precautions ] .

Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1 [see Dosage and Administration and Warnings and Precautions ] .

For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next COLUMVI infusion.

Preparation into an Intravenous Bag This section describes preparation of all doses of COLUMVI into an intravenous bag. For preparation instructions for the 2.5 mg dose into an intravenous syringe, see subsection 2.6 [see Dosage and Administration ] . Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Use aseptic technique when preparing the COLUMVI diluted solution for intravenous infusion. Dilution for Intravenous Bag Infusion Determine the dose, total volume of COLUMVI solution, and the number of COLUMVI vials needed (see Table 7 ).

Select an appropriate size infusion bag of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection (see Table 7 ). COLUMVI diluted with 0.9% Sodium Chloride Injection is compatible with intravenous infusion bags composed of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP) or polyolefin. COLUMVI diluted with 0.45% Sodium Chloride Injection is compatible with intravenous infusion bags composed of PVC.

Prepare the infusion bag by withdrawing and discarding the volume from the infusion bag according to Table 7 . Withdraw the required volume of COLUMVI from the vial(s) using a sterile needle and syringe and dilute into the infusion bag to a final concentration of 0.1 mg/mL to 0.6 mg/mL according to Table 7 . [See table below.] 10 mL 10 mL 100 mL 30 mg 50 mL 30 mL 30 mL 50 mL 100 mL 30 mL 30 mL 100 mL Discard any unused COLUMVI left in the vial.

Gently invert the infusion bag to mix the solution, in order to avoid excess foaming. Do not shake.

Preparation of 2.5 mg Dose into an Intravenous Syringe This section describes the alternative method of preparation of the 2.5 mg dose of COLUMVI into an intravenous syringe. For preparation instructions for all doses into an intravenous infusion bag, see subsection 2.5 [see Dosage and Administration ] . Preparation Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

COLUMVI is a colorless clear solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles. Use aseptic technique when preparing the COLUMVI diluted solution for intravenous syringe infusion. Dilution for Intravenous Syringe Infusion (Alternative Method for 2.5 mg Dose Only) Draw 22.5 mL of 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection into a 30 mL syringe composed of PP (see Table 8 ).

Withdraw 2.5 mL of COLUMVI from the vial using a sterile needle into a second syringe (see Table 8 ). Discard any unused COLUMVI left in the vial. Attach a connector to the two syringes and transfer COLUMVI into the 30 mL syringe. The final concentration of COLUMVI should be 0.1 mg/mL. [See table below.] Disconnect the syringes.

Draw air into the syringe containing the COLUMVI diluted solution and close. Gently invert the syringe to mix the solution, in order to avoid excessive foaming. Do not shake. Remove air bubbles from the syringe before administration.

Storage and Administration Storage of Diluted Product Immediately use diluted COLUMVI solution. If not used immediately, the diluted solution can be stored: Refrigerated at 2°C to 8°C (36°F to 46°F) for up to 64 hours, or At room temperature up to 25°C (77°F) for up to 4 hours. Do not freeze the diluted infusion solution.

Discard diluted infusion solution if storage time exceeds these limits. COLUMVI Administration Administer COLUMVI as an intravenous infusion only through a dedicated infusion line that includes a sterile 0.2-micron in-line filter using an intravenous infusion pump or syringe pump. Prime the infusion line with the diluted infusion solution.

No incompatibilities have been observed with infusion sets with product-contacting surfaces of polyurethane (PUR), PVC, PE, polybutadiene (PBD), polyetherurethane (PEU), polycarbonate (PC), silicone, polytetrafluoroethylene (PTFE), or acrylonitrile butadiene styrene (ABS), and in-line filter membranes composed of polyethersulfone (PES) or polysulfone.

See Table 1 for duration of infusion. The maximum time for the administration of the diluted infusion solution may be extended up to 8 hours (see Table 4 ). To ensure the entire dose of COLUMVI is administered, replace the empty infusion bag or syringe with an infusion bag or syringe containing 0.9% Sodium Chloride Injection or 0.45% Sodium Chloride Injection connected to the same infusion line.

Continue the infusion at the same rate until the recommended infusion duration is reached according to Table 1 . Do not mix COLUMVI with other drugs.