Home › Drugs › Tarlatamab-Dlle

Tarlatamab-Dlle

FDA Drug Information • Also known as: Imdelltra (Amg757)

Brand Names
Imdelltra (Amg757)
Dosage Form
KIT
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA. Initiate IMDELLTRA using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and Warnings and Precautions (5.1) ] . Neurologic toxicity and immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA until ICANS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) and Warnings and Precautions (5.2) ] . WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME See full prescribing information for complete boxed warning . Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA. Initiate treatment with the IMDELLTRA using step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA until CRS resolves or permanently discontinue based on severity. ( 2.5 , 5.1 ) Neurologic toxicity and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), including life-threatening or fatal reactions, can occur in patients receiving IMDELLTRA. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA until ICANS resolves or permanently discontinue based on severity. ( 2.5 , 5.2 )

Description

11 DESCRIPTION Tarlatamab-dlle is a bispecific DLL3-directed CD3 T-cell engager that binds to DLL3 expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T cells. Tarlatamab-dlle is produced using recombinant DNA technology in Chinese hamster ovary cells. It consists of 982 amino acids and has a molecular weight of approximately 105 kilodaltons. IMDELLTRA (tarlatamab-dlle) for injection is supplied as a sterile, preservative-free, white to slightly yellow, lyophilized powder in a single-dose vial for reconstitution and further dilution. Each 1 mg vial contains tarlatamab-dlle (1 mg), glutamic acid (0.72 mg), polysorbate 80 (0.04 mg), sucrose (37.1 mg), and sodium hydroxide to adjust pH to 4.2. After reconstitution with 1.3 mL of Sterile Water for Injection the resulting concentration is 0.9 mg/mL IMDELLTRA. Each 10 mg vial contains tarlatamab-dlle (10 mg), glutamic acid (3.7 mg), polysorbate 80 (0.2 mg), sucrose (194.4 mg), and sodium hydroxide to adjust pH to 4.2. After reconstitution with 4.4 mL of Sterile Water for Injection the resulting concentration is 2.4 mg/mL IMDELLTRA. IV Solution Stabilizer is supplied as a sterile, preservative-free, colorless to slightly yellow, clear solution. Each vial of IV Solution Stabilizer contains citric acid monohydrate (36.75 mg), lysine hydrochloride (1598.8 mg), polysorbate 80 (7 mg), sodium hydroxide to adjust pH to 7.0, and water for injection.

What Is Tarlatamab-Dlle Used For?

1 INDICATIONS AND USAGE IMDELLTRA is indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. IMDELLTRA is a bispecific delta-like ligand 3 (DLL3)-directed CD3 T- cell engager indicated for the treatment of adult patients with extensive stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum - based chemotherapy. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Administer as an intravenous infusion over 1 hour. ( 2.2 ) Administer IMDELLTRA according to the step - up dosing schedule in Table 1 to reduce the risk of cytokine release syndrome. ( 2.2 ) Administer concomitant medications as recommended. ( 2.3 ) 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. Recommend patients to remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from the start of the infusion with IMDELLTRA following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver. ( 2.2 ) See Full Prescribing Information for instructions on preparation and administration. ( 2.2 , 2.6 ) 2.1 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 (2.2) ] . 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 (5.1) ] . 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 (2.3) ] . 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 (2.5) 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. 2.2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome (CRS) [see Warnings and Precautions (5.1) ] Neurologic Toxicity Including ICANS [see Warnings and Precautions (5.2) ] Cytopenias [see Warnings and Precautions (5.3) ] Infections [see Warnings and Precautions (5.4) ] Hepatotoxicity [see Warnings and Precautions (5.5) ] Hypersensitivity [see Warnings and Precautions (5.6) ] The most common adverse reactions (> 20%) were cytokine release syndrome, fatigue, decreased appetite, anemia, dysgeusia, pyrexia, constipation, musculoskeletal pain, and nausea. The most common (≥ 5%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes, decreased sodium, decreased total neutrophils, and increased uric acid. To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) 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. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to intravenous IMDELLTRA, as a single agent, at the recommended dosage of IMDELLTRA 1 mg on Cycle 1 Day 1 followed by 10 mg on Days 8 and 15, and then every 2 weeks until disease progression or intolerable toxicity in 473 patients with small cell lung cancer enrolled in three clinical trials: DeLLphi-300, DeLLphi-301 and DeLLphi-304. Among 473 patients who received IMDELLTRA, 40% were exposed for 6 months or longer and 19% were exposed for greater than one year. The most common (≥ 20%) adverse reactions were CRS (57%), fatigue (48%), decreased appetite (38%), dysgeusia (34%), pyrexia (33%), constipation (31%), musculoskeletal pain (31%), and nausea (25%). The most common (≥ 5%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (43%), decreased sodium (12%), decreased total neutrophils (9%), and increased uric acid (6%). Extensive Stage Small Cell Lung Cancer The safety of IMDELLTRA was evaluated in 252 patients in DeLLphi-304, a multicenter, randomized, open label trial in patients with extensive stage small cell lung cancer (ES- SCLC) with disease progression following treatment with platinum-based chemotherapy with or without an anti-PD-(L)1 antibody [see Clinical Studies (14.1) ]. Patients received IMDELLTRA (n=252) or investigator's choice or investigator's choice of topotecan [n=176], lurbinectedin [n=45] or amrubicin [n=23]. Among patients who received IMDELLTRA, 41% were exposed for 6 months or longer and 18% were exposed for greater than one year. The demographic characteristics of patients who received IMDELLTRA were: median age 64 years (range: 20 to 86); 71% male; 60% White, 38 % Asian, 0.8% Black or African American; and 4.8% were of Hispanic or Latino ethnicity. Serious adverse reactions occurred in 52% of patients who received IMDELLTRA. Serious adverse reactions in >3% of patients included CRS (17%), pyrexia (6%), pneumonia (5%) and ICANS (3.6%). Fatal adverse reactions occurred in 8% of patients who received IMDELLTRA, including one fatal adverse reaction of ICANS (0.4%). Fatal adverse reactions occurring in more than one patient included pneumonia (1.6%), cardio-respiratory arrest (1.6%), and sepsis (0.8%). Permanent discontinuation of IMDELLTRA due to an adverse reaction occurred in 6% of patients. Adverse reactions which resulted in permanent discontinuation of IMDELLTRA in > 1% of patients included pneumonia (1.2%). Dosage interruptions of IMDELLTRA due to an adverse reaction occurred in 38% of patients. Adverse reactions which required dosage interruption in ≥ 2% of patients included neutropenia (5%), fatigue (4.4%), pneumonia (4%), decreased appetite (2.8%), COVID-19 (2%). Table 13...

Contraindications

4 CONTRAINDICATIONS None . None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action, IMDELLTRA may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of IMDELLTRA in pregnant women to inform a drug-associated risk. In an animal reproduction study, a murine surrogate molecule administered intravenously to pregnant mice crossed the placental barrier . Tarlatamab-dlle causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) and proteins comprising IgG-derived fragment crystallizable (Fc) domains are known to cross the placental barrier; therefore, IMDELLTRA has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to the fetus. 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. Data Animal Data Animal reproduction studies have not been conducted with tarlatamab-dlle. In an embryo-fetal developmental toxicity study, a murine surrogate molecule was administered intravenously to pregnant mice during the period of organogenesis. The surrogate molecule crossed the placental barrier and did not cause maternal toxicity, embryo-fetal toxicity or teratogenicity.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied IMDELLTRA (tarlatamab-dlle) for injection is a sterile, preservative-free, white to slightly yellow, lyophilized powder supplied as follows: 1 mg package (NDC 55513-059-01) contains 1 single-dose vial of 1 mg IMDELLTRA and 2 vials of 7 mL IV Solution Stabilizer. 10 mg package (NDC 55513-077-01) contains 1 single-dose vial of 10 mg IMDELLTRA and 2 vials of 7 mL IV Solution Stabilizer. 16.2 Storage and Handling Store IMDELLTRA and IV Solution Stabilizer (IVSS) vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Do not freeze. IMDELLTRA and IV Solution Stabilizer (IVSS) vials may be kept at room temperature between 20°C to 25°C (68°F to 77°F) for up to 24 hours in the original carton to protect from light.

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.