Tarlatamab

Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Important Dosage and Administration Information Administer IMDELLTRA according to the step-up dose and schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome (CRS) [see Dosage and Administration ] . Evaluate complete blood count, liver enzymes and bilirubin prior to administration of all doses of IMDELLTRA up through Cycle 5 Day 15 and then prior to administration of IMDELLTRA on Day 1 of each cycle starting with Cycle 6.

More frequent evaluation may be necessary if clinically indicated [see Warnings and Precautions (5.3 , 5.5) ] . Ensure patients are well hydrated prior to administration of IMDELLTRA [see Warnings and Precautions ] . For Cycle 1, administer recommended concomitant medications in Table 3 before and after Cycle 1 Day 1 and Cycle 1 Day 8 IMDELLTRA infusions to reduce the risk of CRS reactions [see Dosage and Administration ] .

IMDELLTRA 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, monitor patients from the start of the IMDELLTRA infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting [see Dosage and Administration and Warnings and Precautions (5.1 , 5.2) ] .

Recommend patients to remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver. Inform both the patient and the caregiver on the signs and symptoms of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) prior to discharge.

Recommended Dosage and Administration Administer IMDELLTRA as an intravenous infusion for one hour. The recommended step-up dose and schedule for IMDELLTRA is provided in Table 1. Administer step-up dose and schedule on Cycle 1 Day 1 to reduce the incidence and severity of CRS. After step-up dose and schedule on Cycle 1 Day 1, administer IMDELLTRA every 2 weeks until disease progression or unacceptable toxicity. [See table below.] Administration The intravenous (IV) catheter for concomitant medications administration can be used to administer the IMDELLTRA infusion.

To ensure patency, flush the IV catheter over 3 to 5 minutes using 0.9% Sodium Chloride for Injection. Administer the reconstituted and diluted IMDELLTRA as a 1-hour intravenous infusion at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm. Flush the IV-line upon completion of the IMDELLTRA infusion.

Table 2 provides the infusion duration and rate. [See table below.]

Recommended Concomitant Medications for IMDELLTRA Administration for Cycle 1 Day 1 and Cycle 1 Day 8 Administer recommended concomitant medications for IMDELLTRA during Cycle 1 Day 1 and Cycle 1 Day 8 as presented in Table 3 to reduce the risk of CRS [see Warnings and Precautions ] . [See table below.]

Preparation Material Compatibility Information IV bags composed of ethyl vinyl acetate (EVA), polyolefin, and polyvinyl chloride (PVC) have been shown to be compatible with IMDELLTRA at the specified administration conditions. IV line and catheter materials composed of polyolefin, PVC, and polyurethane have been shown to be compatible with IMDELLTRA at the specified administration conditions.

The use of Closed System Transfer Device (CSTD) is not recommended due to potential wrong dose medication error risk. Amgen has not performed compatibility testing of vial adaptor CSTDs with IMDELLTRA. Step 1: Reconstitute IMDELLTRA with Sterile Water for Injection Table 8 provides the required amount of sterile water for injection required to reconstitute IMDELLTRA 1 mg and 10 mg vials.

Do not use IV Solution Stabilizer (IVSS) to reconstitute IMDELLTRA . The IV Solution Stabilizer (IVSS) is used to coat the intravenous bag prior to addition of reconstituted IMDELLTRA to prevent adsorption of IMDELLTRA to IV bags and IV tubing. [See table below.] Using a needle and syringe filled with the required amount of sterile water, inject the sterile water against the glass vial.

Avoid injecting the water directly onto the powder to prevent foaming. Gently swirl the contents to mix. Do not shake. Inspect parenteral drug products for particulate matter and discoloration prior to administration. Inspect that the solution is clear to opalescent, colorless to slightly yellow. Do not use if the solution is cloudy or has particulates.

Further dilute reconstituted IMDELLTRA. The reconstituted IMDELLTRA must be further diluted within 4 hours of reconstitution or discarded. Prepare the infusion bag: Steps 2 to 5 Step 2 : Withdraw 0.9% Sodium Chloride for Injection Using a 250 mL prefilled bag of 0.9% Sodium Chloride for Injection, withdraw the amount of sodium chloride specified in Table 9 and discard. [See table below.] Step 3: Add IV Solution Stabilizer to the infusion bag Inject 13 mL of IV Solution Stabilizer (IVSS) into the 250 mL 0.9% Sodium Chloride infusion bag , see Table 10 .

Gently mix the contents of the infusion bag to avoid foaming. Do not shake. [See table below.] 10 mg 10 mg 13 mL Step 4: Dilute the reconstituted IMDELLTRA into the infusion bag Transfer the required volume of reconstituted IMDELLTRA listed in Table 11 to the infusion bag (containing IV Solution Stabilizer) . NOTE: The final concentrations for the different strength vials are NOT the same following reconstitution and further dilution. [See table below.] Gently mix the contents of the bag.

Do not shake. Step 5: Remove air from IV bag Remove air from the prepared IV bag using an empty syringe to avoid foaming. Step 6: Prime IV tubing Prime intravenous tubing with either 0.9% Sodium Chloride for Injection or with the final prepared product. See Table 12 for maximum storage time of prepared IMDELLTRA infusion.

Prepared IMDELLTRA Infusion Bag Storage Requirements Administer reconstituted and diluted IMDELLTRA immediately. Table 12 displays the maximum storage time for the prepared IMDELLTRA infusion bag. Maximum storage time includes total duration from the time of reconstitution of the vial of IMDELLTRA to the end of the infusion. [See table below.]