Brand name: Imdelltra
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 10, 2024. Written by ASHP.

Introduction

Tarlatamab-dlle, a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, is an antineoplastic agent.

Uses for Tarlatamab-dlle

Tarlatamab-dlle has the following uses:

Tarlatamab-dlle 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.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tarlatamab-dlle Dosage and Administration

General

Tarlatamab-dlle is available in the following dosage form(s) and strength(s):

For injection: 1 mg of lyophilized powder in a single-dose vial for reconstitution and further dilution.

For injection: 10 mg of lyophilized powder in a single-dose vial for reconstitution and further dilution.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Administer as an IV infusion over 1 hour at a constant flow rate using an infusion pump; must reconstitute and dilute commercially available drug prior to use.

• Administer by a qualified healthcare professional with appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS) and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS).

• Administer tarlatamab-dlle according to the step-up dosing schedule in Table 1 to reduce the risk of cytokine release syndrome.

• Administer recommended concomitant medications before and after Cycle 1 infusions as described in the prescribing information.

• Monitor patients from the start of the tarlatamab-dlle 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 tarlatamab-dlle following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.

• See Full Prescribing Information for instructions on preparation and administration, and dosage modification recommendations for adverse reactions.

Cautions for Tarlatamab-dlle

Contraindications

• None.

Warnings/Precautions

Cytokine Release Syndrome

Tarlatamab-dlle can cause cytokine release syndrome (CRS) including serious or life-threatening reactions.

In the pooled safety population, CRS occurred in 55% of patients who received tarlatamab-dlle, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3, and 0.5% Grade 4. Recurrent CRS occurred in 24% of tarlatamab-treated patients including 18% Grade 1 and 6% Grade 2.

Most events (43%) of CRS occurred after the first dose with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3%, and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of tarlatamab-dlle was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of tarlatamab-dlle was 14.6 hours (range: 2 to 566 hours).

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).

Administer tarlatamab-dlle following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 infusions as described in the prescribing information to reduce the risk of CRS. Administer tarlatamab-dlle in an appropriate healthcare facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of tarlatamab-dlle.

Closely monitor patients for signs and symptoms of CRS during treatment with tarlatamab-dlle. At the first sign of CRS, immediately discontinue the infusion, evaluate the patient for hospitalization, and institute supportive care based on severity. Withhold or permanently discontinue tarlatamab-dlle based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur.

Neurologic Toxicity Including ICANS

Tarlatamab-dlle can cause serious or life-threatening neurologic toxicity, including ICANS.

In the pooled safety population, neurologic toxicity including ICANS, occurred in 47% of patients who received tarlatamab-dlle, including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).

ICANS occurred in 9% of tarlatamab-dlle-treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following cycle 2 day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of tarlatamab-dlle was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of tarlatamab-dlle. The median time to resolution of ICANS was 33 days (range: 1 to 93 days).

The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.

Patients receiving tarlatamab-dlle are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve.

Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold tarlatamab-dlle or permanently discontinue based on severity.

Cytopenias

Tarlatamab-dlle can cause cytopenias including neutropenia, thrombocytopenia, and anemia.

In the pooled safety population, decreased neutrophils occurred in 12%, including 6% Grade 3 or 4, of tarlatamab-dlle-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% of patients, including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% of patients, including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with tarlatamab-dlle.

Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with tarlatamab-dlle, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue the drug.

Infections

Tarlatamab-dlle can cause serious infections, including life-threatening and fatal infections.

In the pooled safety population, infections including opportunistic infections occurred in 41% of patients who received tarlatamab-dlle. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%). Monitor patients for signs and symptoms of infection prior to and during treatment with tarlatamab-dlle and treat as clinically indicated. Withhold or permanently discontinue the drug based on severity.

Hepatotoxicity

Tarlatamab-dlle can cause hepatotoxicity.

In the pooled safety population, elevated ALT occurred in 42% with Grade 3 or 4 ALT elevation occurring in 2.1% of tarlatamab-dlle-treated patients. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients, with Grade 3 or 4 total bilirubin elevations occurring in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with tarlatamab-dlle, before each dose, and as clinically indicated. Withhold tarlatamab-dlle or permanently discontinue based on severity.

Hypersensitivity

Tarlatamab-dlle can cause severe hypersensitivity reactions.

Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with tarlatamab-dlle and manage as clinically indicated. Withhold or consider permanent discontinuation of therapy based on severity.

Embryo-fetal Toxicity

Based on its mechanism of action, tarlatamab-dlle may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with tarlatamab-dlle and for 2 months after the last dose.

Specific Populations

Pregnancy

Based on its mechanism of action, tarlatamab-dlle may cause fetal harm when administered to a pregnant woman. There are no available data on the use of tarlatamab-dlle 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, tarlatamab-dlle 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.

Lactation

There are no data on the presence of tarlatamab-dlle in human milk or the effects on the breastfed child or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to tarlatamab-dlle are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with tarlatamab-dlle and for 2 months after the last dose.

Females and Males of Reproductive Potential

Tarlatamab-dlle may cause fetal harm when administered to a pregnant woman.

Verify pregnancy status of females of reproductive potential prior to initiating tarlatamab-dlle.

Advise females of reproductive potential to use effective contraception during treatment with tarlatamab-dlle and for 2 months after the last dose.

Pediatric Use

The safety and effectiveness of tarlatamab-dlle have not been established in pediatric patients.

Geriatric Use

Of the 187 patients with small cell lung cancer (SCLC) who received tarlatamab-dlle 10 mg as a single agent, 54% were 65 years of age or older and 12% were 75 years of age or older. No overall differences in tarlatamab pharmacokinetics or safety were observed between older patients (≥ 65 years of age) and younger patients. Clinical studies of tarlatamab-dlle did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.

Common Adverse Effects

The most common adverse reactions (≥20%) were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.

The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, increased uric acid, decreased total neutrophils, decreased hemoglobin, increased activated partial thromboplastin time, decreased potassium, increased aspartate aminotransferase, decreased white blood cells, decreased platelets, and increased alanine aminotransferase.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Tarlatamab-dlle is a bispecific T-cell engager that binds to delta-like ligand 3 (DLL3) expressed on the surface of cells, including tumor cells, and CD3 expressed on the surface of T-cells. Tarlatamab-dlle causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells. Tarlatamab-dlle exhibits anti-tumor activity in mouse models of SCLC.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).

• Advise patients of the risk of Cytokine Release Syndrome (CRS), and to immediately contact their healthcare provider for signs and symptoms, including pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting.

• Advise patients that they should be monitored from the start of the tarlatamab-dlle infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.

• Advise patients to remain within 1-hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with tarlatamab-dlle following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.

• Discuss the signs and symptoms associated with Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms, such as encephalopathy, confusion, delirium, seizure, ataxia, weakness or numbness of arms and legs, tremor, and headache. Advise patients who experience neurologic toxicity or symptoms of ICANS to refrain from driving or operating heavy or potentially dangerous machinery and engaging in hazardous occupations or activities during treatment with tarlatamab-dlle.

• Discuss the signs and symptoms associated with cytopenias, including neutropenia and febrile neutropenia, anemia, and thrombocytopenia. Inform patients that they will need to undergo lab tests to monitor blood counts. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of cytopenias.

• Discuss the signs and symptoms of infections. Advise patients of the risk of serious infections, and to immediately contact their healthcare provider for signs or symptoms of infections.

• Discuss the signs and symptoms of hepatotoxicity. Inform patients that they will need to undergo lab tests to monitor liver function. Advise patients to immediately contact their healthcare provider for signs and symptoms of liver dysfunction.

• Discuss the signs and symptoms of allergic reactions. Advise patients to immediately seek medical attention for any signs and symptoms of severe reactions.

• Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant. Advise females of reproductive potential to use effective contraception during treatment with tarlatamab-dlle and for 2 months after the last dose.

• Advise women not to breastfeed during treatment with tarlatamab-dlle and for 2 months after the last dose.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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