Tarlatamab-dlle, a bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, is an antineoplastic agent.1, 10
Tarlatamab-dlle is used 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, 10 Tarlatamab-dlle has been designated an orphan drug by FDA for treatment of small cell lung cancer.7
Efficacy and safety of tarlatamab-dlle for the treatment of small-cell lung cancer (SCLC) in patients with disease progression during or after one previous line of platinum-containing therapy were evaluated in a multinational, phase 3, multicenter, open-label, randomized controlled trial (DeLLphi-304).1, 3 Patients were assigned in a 1:1 ratio to receive tarlatamab-dlle or standard-of-care chemotherapy selected by the investigator (topotecan, lurbinectedin, or amrubicin depending on the country).3 Randomization was stratified according to previous exposure to programmed death ligand 1 (PD-L1) or programmed death 1 (PD-1) inhibitors, chemotherapy-free interval, presence of brain metastases, and investigator's choice of chemotherapy.3 Tarlatamab-dlle was administered as a 60-minute IV infusion that was initiated with a step-up dose of 1 mg on day 1 of cycle 1, followed by 10 mg on days 8 and 15 of cycle 1 and then 10 mg every 2 weeks thereafter in 28-day cycles.3 Chemotherapy was administered in 21-day cycles.3 Treatment was continued until radiologic disease progression, unacceptable toxicity, withdrawal of consent, or death.3
Patients 18 years of age or older with SCLC that had progressed during or after first-line platinum-based treatment and an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 were eligible for the study; patients were also required to have at least one measurable lesion per Response Criteria in Solid Tumors (RECIST v1.1).3 The primary end point was overall survival, which was defined as the time from randomization to death from any cause.3 A total of 590 patients were randomized to receive tarlatamab-dlle or chemotherapy.3 Among patients in the chemotherapy group, 185 (73%) received topotecan, 47 (18%) received lurbinectedin, and 23 (9%) received amrubicin.3 Seventy-one percent of patients received previous PD-L1 or PD-1 inhibitor therapy and 44% had platinum-resistant disease, as defined by disease progression after a chemotherapy-free interval of <90 days after the final dose of first-line platinum-based chemotherapy.3 Tarlatamab significantly improved overall survival compared with chemotherapy at a median duration of follow-up of 11.2 months in the tarlatamab group and 11.7 months in the chemotherapy group.1 A total of 111 deaths occurred in the tarlatamab-dlle group compared with 152 deaths in the chemotherapy group.1, 3 Median overall survival was 13.6 months with tarlatamab-dlle and 8.3 months with chemotherapy.1, 3 Progression-free survival also was significantly improved with tarlatamab-dlle (median of 4.2 months) compared with chemotherapy (median of 3.2 months).1
Tarlatamab was initially approved under accelerated approval based on the results of a phase 2, open-label, international trial evaluating the drug as a single agent in adults with relapsed or refractory SCLC previously treated with ≥2 lines of therapy.1, 4 A total of 99 patients received tarlatamab-dlle in a step-up dose of 1 mg on day 1 of cycle 1, followed by 10 mg on days 8, 15, and every 2 weeks thereafter in 28-day cycles until disease progression or unacceptable toxicity occurred.4 Dexamethasone 8 mg was administered IV before tarlatamab-dlle was given on day 1 and day 8 of cycle 1, and prophylactic hydration (1 L of normal saline) was administered IV after each dose in cycle 1.4 Tumor assessments were performed every 6 weeks for the first year and then every 12 weeks thereafter.4 Eligible patients had histologically or cytologically confirmed SCLC that had relapsed after, or was refractory to, one platinum-based treatment regimen and at least one other line of therapy, measurable lesions as defined by the RECIST version 1.1, and an ECOG peformance-status grade of 0 or 1.4 The main efficacy outcome measures were overall response rate and duration of response.1 The overall response rate was 40% (2 patients had a complete response and 38 patients had a partial response).4, 9, 10 Among responders, the median duration of response was 9.7 months; 68 patients had a duration of response ≥6 months and 40 patients had a duration of response ≥12 months.1 In 27 patients with platinum-resistant disease, the overall response rate was 52% and in 42 patients with platinum-sensitive disease, the overall response rate was 31%.1
Small-cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma occurring predominantly in current or former smokers and has a poor prognosis.8 The majority of cases are diagnosed as extensive stage disease.9, 10 The treatment options for SCLC are determined by the stage of cancer and other factors including overall health and lung function.5 Patients diagnosed with ES-SCLC may be prescribed chemotherapy with or without immunotherapy.5
The American Society of Clinical Oncology (ASCO) has published guidelines on systemic therapy for SCLC.6 Topotecan, lurbinectedin, and tarlatamab-dlle are recommended for the treatment of relapsed SCLC.6, 9, 10 Topotecan and lurbinectedin are expected to have a differential tumor response based on a patient's sensitivity to platinum-based chemotherapy.9 The response of tarlatamab-dlle is not expected to be impacted by sensitivity to platinum-based chemotherapy due to its mechanism of action.9 Tarlatamab-dlle may be used for the treatment of relapsed SCLC if there is disease progression after receipt of platinum-based chemotherapy.6
Dispensing and Administration Precautions
Tarlatamab-dlle is administered via IV infusion only.1
IV bags composed of ethyl vinyl acetate (EVA), polyolefin, and polyvinyl chloride (PVC) have been shown to be compatible with tarlatamab-dlle at the specified administration conditions.1
IV line and catheter materials composed of polyolefin, PVC, and polyurethane have been shown to be compatible with tarlatamab-dlle at the specified administration conditions.1
The use of a closed system transfer device (CSTD) is not recommended due to potential wrong dose medication error risk.1 Compatibility testing of vial adaptor CSTDs with tarlatamab-dlle has not been conducted.1
The IV catheter for concomitant medication administration can be used to administer the tarlatamab-dlle infusion.1
To ensure patency, flush the IV catheter over 3 to 5 minutes using 0.9% sodium chloride injection.1
Initiate tarlatamab-dlle therapy according to the step-up dose and schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome (CRS).1
After step-up dose and schedule on cycle 1 day 1, administer tarlatamab-dlle every 2 weeks until disease progression or unacceptable toxicity.1
Store tarlatamab-dlle and IV solution stabilizer (IVSS) vials refrigerated at 2-8°C in the original carton to protect from light until time of use.1 Do not freeze.1 Tarlatamab-dlle and IVSS vials may be kept at room temperature between 20-25°C for up to 24 hours in the original carton to protect from light.1
Reconstitute tarlatamab-dlle lyophilized powder with sterile water for injection.1 Do not use IVSS to reconstitute tarlatamab-dlle.1 The IVSS is used to coat the IV bag prior to addition of reconstituted tarlatamab-dlle to prevent adsorption of the drug to IV bags and tubing.1
Reconstitute tarlatamab-dlle 1 mg vial by adding 1.3 mL of sterile water to result in a tarlatamab-dlle 0.9 mg/mL concentration.1
Reconstitute tarlatamab-dlle 10 mg vial by adding 4.4 mL of sterile water to result in a tarlatamab-dlle 2.4 mg/mL concentration.1
Using a needle and syringe filled with the required amount of sterile water, inject the sterile water against the glass vial.1 Avoid injecting the water directly onto the powder to prevent foaming.1
Gently swirl the contents to mix.1 Do not shake.1
Inspect the solution to ensure that it is clear to opalescent, colorless to slightly yellow.1 Do not use if the solution is cloudy or has particulates.1
Must further dilute the reconstituted solution within 4 hours of reconstitution or discard.1 Prepare the final infusion solution in a 250 mL IV bag containing 0.9% sodium chloride injection.1
Each vial contains an overfill to allow for withdrawal of 1.1 mL (for the 1 mg tarlatamab-dlle vial) or 4.2 mL (for the 10 mg tarlatamab-dlle vial) after reconstitution to ensure delivery at the stated concentration of labeled vial strength.1
To prepare the infusion solution for a 1-mg dose, withdraw and discard 14 mL of 0.9% sodium chloride from the 250 mL IV bag.1 Add 13 mL of IVSS to the IV bag; gently mix the contents and do not shake, then transfer 1.1 mL of reconstituted drug from the 1-mg tarlatamab-dlle vial to the 250 mL IV bag.1 Gently mix contents of bag; do not shake.1
To prepare the infusion solution for a 10-mg dose, withdraw and discard 17 mL of 0.9% sodium chloride from the 250 mL IV bag.1 Add 13 mL of IVSS to the IV bag; gently mix the contents and do not shake, then transfer 4.2 mL of reconstituted drug from the 10-mg tarlatamab-dlle vial to the 250 mL IV bag.1 Gently mix contents of bag; do not shake.1
The final concentrations for the different vial strengths are not the same following reconstitution and further dilution.1 Remove air from the prepared IV bag using an empty syringe to avoid foaming.1
Prime IV tubing with either 0.9% sodium chloride for injection or with the final prepared product.1
Administer reconstituted and diluted tarlatamab-dlle immediately.1
The maximum storage time (defined as total duration from the time of reconstitution to the end of the infusion) is 8 hours at room temperature (i.e., 20-25°C) or 7 days refrigerated (i.e., 2-8°C).1
Discard the prepared tarlatamab-dlle infusion bag after maximum storage time (i.e., from time of reconstitution).1
If refrigerated, allow prepared tarlatamab-dlle infusion bag to come to room temperature prior to administration and complete the infusion within 8 hours (including preparation and infusion time).1 Do not re-refrigerate prepared infusion bag.1
Administer reconstituted and diluted tarlatamab-dlle as a 1 hour IV infusion at a constant flow rate of 250 mL/hour using an infusion pump.1
The pump should be programmable, lockable, non-elastomeric, and have an alarm.1
The recommended step-up dose and schedule of tarlatamab-dlle in adults is provided in Table 1.1 Administer step-up dose and schedule on cycle 1 day 1 to reduce the incidence and severity of cytokine release syndrome (CRS).1 After step-up dose and schedule in cycle 1, administer tarlatamab-dlle at a dose of 10 mg on day 1 and day 15 of subsequent cycles until disease progression or unacceptable toxicity.1
Dosing Schedule | Day | Dose of Tarlatamab-dlle |
|---|---|---|
Step-up dose and schedule cycle 1 | Day 1 | Step-up dose: 1 mg |
Step-up dose and schedule cycle 1 | Day 8 | 10 mg |
Step-up dose and schedule cycle 1 | Day 15 | 10 mg |
Administer recommended concomitant medications before and after cycle 1 day 1 and cycle 1 day 8 tarlatamab-dlle infusions (see Premedication and Prophylaxis under Dosage and Administration).1
If a dose of tarlatamab-dlle is delayed, restart based on the recommendations in Table 2.1
Last Dose Administered | Time Since the Last Dose Administered | Recommendation |
|---|---|---|
1 mg on cycle 1 day 1 | ≤2 weeks (≤14 days) | Administer tarlatamab-dlle 10 mg, then resume with the planned dose and schedule. |
1 mg on cycle 1 day 1 | >2 weeks (>14 days) | Administer tarlatamab-dlle step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dose and schedule. |
10 mg on cycle 1 day 8 | ≤3 weeks (≤21 days) | Administer tarlatamab-dlle 10 mg, then resume with the planned dose and schedule. |
10 mg on cycle 1 day 8 | >3 weeks (>21 days) | Administer tarlatamab-dlle step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dose and schedule. |
10 mg on cycle 1 day 15 and subsequent cycles every 2 weeks thereafter | ≤4 weeks (≤28 days) | Administer tarlatamab-dlle 10 mg, then resume with the planned dose and schedule. |
10 mg on cycle 1 day 15 and subsequent cycles every 2 weeks thereafter | >4 weeks (>28 days) | Administer tarlatamab-dlle step-up dose 1 mg. If tolerated, increase to 10 mg 1 week later. Then resume with the planned dose and schedule. |
Administer recommended concomitant medications before and after cycle 1 day 1 and cycle 1 day 8 tarlatamab-dlle infusions and monitor patients accordingly (see Premedication and Prophylaxis under Dosage and Administration).1
Dosage Modifications for Toxicity
No dose reduction for tarlatamab-dlle is recommended.1 See Tables 3 and 4 for recommended management of cytokine release syndrome (CRS) and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS), respectively, and Table 5 for cytopenias, infections, and other adverse reactions.1
See Table 2 for recommendations on restarting tarlatamab-dlle after dose delays.1
Guidelines for the management of neurologic toxicity are based on the Immune Effector Cell-Associated Encephalopathy (ICE) score.1 The manufacturer recommends that ICE assessments be performed if the patient is arousable.1 Assess orientation (oriented to year, month, city, hospital=4 points); naming (names 3 objects, e.g., point to clock, pen, button=3 points); following commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue"= 1 point); writing (ability to write a standard sentence=1 point); and attention (count backwards from 100 by ten=1 point).1 If patient is unarousable and unable to perform ICE assessment (Grade 4 ICANS)=0 points.1
CRS Grade | Defining Symptoms | Tarlatamab-dlle Dosage Modification | Management |
|---|---|---|---|
Grade 1 | Symptoms require symptomatic treatment only (e.g., fever ≥100.4° without hypotension or hypoxia). | Withhold tarlatamab-dlle until event resolves, then resume tarlatamab-dlle at the next scheduled dose. | Administer symptomatic treatment (e.g., acetaminophen) for fever. Consider dexamethasone 4 mg to 10 mg oral or IV (or equivalent). Taper steroids per standard of care guidelines. |
Grade 2 | Symptoms require and respond to moderate intervention. Fever ≥100.4°F, hypotension responsive to fluids not requiring vasopressors and/or hypoxia requiring low flow nasal cannula or blow-by. | Withhold tarlatamab-dlle until event resolves, then resume tarlatamab-dlle at the next scheduled dose. | Recommend hospitalization for a minimum of 24 hours with cardiac telemetry and pulse oximetry. Administer symptomatic treatment (e.g., acetaminophen) for fever. Administer supplemental oxygen and IV fluids when indicated. Consider dexamethasone (or equivalent) 8 mg oral or IV. Taper steroids per standard of care guidelines. Consider tocilizumab (or equivalent) When resuming the next planned dose, monitor patients from the start of the tarlatamab-dlle infusion for 22 to 24 hours in an appropriate healthcare setting. |
Grade 3 | Severe symptoms defined as temperature ≥100.4°F with hemodynamic instability requiring a vasopressor (with or without vasopressin) and/or worsening hypoxia or respiratory distress requiring high flow nasal cannula (>6 L/minute) or face mask. | Withhold tarlatamab-dlle until the event resolves, then resume tarlatamab-dlle at the next scheduled dose. For recurrent Grade 3 events, permanently discontinue tarlatamab-dlle. | In addition to Grade 2 treatment: Recommend intensive monitoring, e.g., intensive care unit (ICU) care. Administer dexamethasone (or equivalent) 8 mg IV every 8 hours up to 3 doses. Taper steroids per standard of care guidelines. Vasopressor support as needed. High flow oxygen support as needed. Recommend tocilizumab (or equivalent) Prior to the next dose, administer concomitant medications as recommended for cycle 1 day 1 and cycle 1 day 8 (see Premedication and Prophylaxis under Dosage and Administration). When resuming the next planned dose, monitor patients from the start of the tarlatamab-dlle infusion for 22 to 24 hours in an appropriate healthcare setting. |
Grade 4 | Life-threatening symptoms defined as temperature ≥100.4°F with hemodynamic instability requiring multiple vasopressors (excluding vasopressin) and/or worsening hypoxia or respiratory distress despite oxygen administration requiring positive pressure. | Permanently discontinue tarlatamab-dlle. | ICU care. Per Grade 3 treatment. Recommend tocilizumab (or equivalent) |
ICANS Grade | Defining Symptoms | Tarlatamab-dlle Dosage Modifications | Management |
|---|---|---|---|
Grade 1 | ICE score 7-9 with no depressed level of consciousness. | Withhold tarlatamab-dlle until ICANS resolves, then resume tarlatamab-dlle at the next scheduled dose. | Supportive care. |
Grade 2 | ICE score 3-6 and/or mild somnolence awakening to voice. | Withhold tarlatamab-dlle until ICANS resolves, then resume tarlatamab-dlle at the next scheduled dose. | Supportive care. Dexamethasone (or equivalent) 8 to 10 mg oral or IV. Taper steroids per standard of care guidelines. Monitor neurologic symptoms and consider consultation with neurologist and other specialists for further evaluation and management. Monitor patients from the start of the tarlatamab-dlle infusion for 22 to 24 hours following the next dose of tarlatamab-dlle. |
Grade 3 | ICE score 0-2 and/or depressed level of consciousness awakening only to tactile stimulus and/or any clinical seizure focal or generalized that resolves rapidly or nonconvulsive seizures on EEG that resolve with intervention and/or focal or local edema on neuroimaging. | Withhold tarlatamab-dlle until the ICANS resolves, then resume tarlatamab-dlle at the next scheduled dose. If there is no improvement to Grade ≤1 within 7 days permanently discontinue tarlatamab-dlle. For recurrent Grade 3 events, permanently discontinue tarlatamab-dlle. | Recommend intensive monitoring, e.g., ICU care. Consider mechanical ventilation for airway protection. Dexamethasone (or equivalent) 10 mg IV every 6 hours or methylprednisolone (or equivalent) 1 mg/kg IV every 12 hours. Taper steroids per standard of care guidelines. Consider repeat neuroimaging [e.g., computed tomography (CT) or magnetic resonance imaging (MRI)] every 2-3 days if patient has persistent Grade ≥ 3 neurotoxicity. Monitor patients from the start of the tarlatamab-dlle infusion for 22 to 24 hours following the next dose of tarlatamab-dlle. |
Grade 4 | ICE score 0 (patient is unarousable and unable to perform ICE) and/or stupor or coma and/or life-threatening prolonged seizure (>5 minutes) or repetitive clinical or electrical seizures without return to baseline in between and/or diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing or papilledema, cranial nerve VI palsy, or Cushing's triad. | Permanently discontinue tarlatamab-dlle. | ICU care. Consider mechanical ventilation for airway protection. High dose corticosteroids (e.g., methylprednisolone 1000 mg/day in divided doses IV for 3 days). Consider repeat neuroimaging (CT or MRI) every 2-3 days if patient has persistent Grade ≥3 neurotoxicity. Treat convulsive status epilepticus per institutional guidelines. |
Adverse Reactions | Severity | Dosage Modification |
|---|---|---|
Cytopenia | Grade 3 neutropenia | Withhold tarlatamab-dlle until recovery to Grade ≤2. Consider administration of granulocyte colony stimulating factor (G-CSF). Permanently discontinue if recovery to Grade ≤2 does not occur within 3 weeks. |
Cytopenia | Grade 4 neutropenia | Withhold tarlatamab-dlle until recovery to Grade ≤2. Consider administration of G-CSF. Permanently discontinue if recovery to Grade ≤2 does not occur within 1 week. |
Cytopenia | Recurrent Grade 4 neutropenia | Permanently discontinue tarlatamab-dlle. |
Cytopenia | Febrile neutropenia | Withhold tarlatamab-dlle until neutropenia recovers to Grade ≤2 and fever resolves. |
Cytopenia | Hemoglobin <8 g/dL | Withhold tarlatamab-dlle until hemoglobin is ≥8 g/dL. |
Cytopenia | Grade 3 or 4 decreased platelet count | Withhold tarlatamab-dlle until platelet count is Grade ≤2 and no evidence of bleeding. Permanently discontinue if recovery to Grade ≤2 does not occur within 3 weeks. |
Cytopenia | Recurrent Grade 4 decreased platelet count | Permanently discontinue tarlatamab-dlle. |
Infections | All Grades | Withhold tarlatamab-dlle in the step-up phase in patients until infection resolves. |
Infections | Grade 3 | Withhold tarlatamab-dlle during the treatment phase until infection improves to Grade ≤1. |
Infections | Grade 4 | Permanently discontinue tarlatamab-dlle. |
Hepatotoxicity | Grade 3 increased ALT, AST, bilirubin | Withhold tarlatamab-dlle until improved to Grade ≤1. |
Hepatotoxicity | Grade 4 increased ALT, AST, or bilirubin | Permanently discontinue tarlatamab-dlle |
Hepatotoxicity | AST, ALT >3 x ULN with total bilirubin >2 x ULN in the absence of alternative causes | Permanently discontinue tarlatamab-dlle. |
Other Adverse Reactions | Grade 3 or 4 | Withhold tarlatamab-dlle until recovery to Grade ≤1 or baseline. Consider permanently discontinuing if adverse reaction does not resolve within 28 days. Consider permanent discontinuation for Grade 4 events. |
The manufacturer makes no specific dosage recommendations for hepatic impairment.1, 10
The manufacturer makes no specific dosage recommendations for renal impairment.1, 10
The manufacturer makes no specific dosage recommendations for geriatric patients.1, 10
Tarlatamab-dlle can cause cytokine release syndrome (CRS) including life-threatening or fatal reactions and a boxed warning has been included in the prescribing information about this risk.1
In the pooled safety population, CRS occurred in 57% (268 out of 473) of patients who received tarlatamab-dlle, including 39% Grade 1, 15% Grade 2, 1.7% Grade 3, and 0.2% Grade 4.1 Recurrent CRS occurred in 24% of tarlatamab-treated patients including 20% Grade 1 and 3.4% Grade 2; one patient experienced recurrent Grade 3.1
Among the 268 patients who experienced CRS, 73% had CRS after the first dose, 60% had CRS after the second dose, and 15% had CRS following the third or later dose.1 Following the cycle 1 day 1, day 8, and day 15 infusions, 24%, 8%, and 1% of patients experienced Grade ≥2 CRS, respectively.1 From Cycle 2 onwards, 1.5% of patients experienced Grade ≥2 CRS.1 Of the patients who experienced CRS, 31% received steroids and 10% required tocilizumab.1 The median time to onset of all grade CRS from the most recent dose of tarlatamab-dlle was 16 hours (range: start of infusion to 15 days).1 The median time to onset of ≥Grade 2 CRS from the most recent dose of tarlatamab-dlle was 15 hours (range: start of infusion to 15 days).1
Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting.1 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).1
Administer tarlatamab-dlle following the recommended step-up dosing and administer concomitant medications before and after cycle 1 day 1 and cycle 1 day 8 tarlatamab-dlle infusions as described in Table 3 to reduce the risk of CRS infusions.1 Administer tarlatamab-dlle in an appropriate healthcare facility equipped to monitor and manage CRS.1 Ensure patients are well hydrated prior to administration of tarlatamab-dlle.1
Closely monitor patients for signs and symptoms of CRS during treatment with tarlatamab-dlle.1 At the first sign of CRS, immediately discontinue the infusion, evaluate the patient for hospitalization, and institute supportive care based on severity.1 Withhold or permanently discontinue tarlatamab-dlle based on severity.1 Counsel patients to seek medical attention should signs or symptoms of CRS occur.1
Neurologic Toxicity Including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)
Tarlatamab-dlle can cause serious or life-threatening neurologic toxicity, including ICANS, and a boxed warning has been included in the prescribing information about this risk.1
In the pooled safety population, neurologic toxicity occurred in 65% of patients who received tarlatamab-dlle, with Grade 3 or higher events in 7% of patients including fatal events in 0.2%.1 The most frequent neurologic toxicities were dysgeusia (34%), headache (17%), peripheral neuropathy (9%), dizziness (9%), and insomnia (8%).1
The incidence of signs and symptoms consistent with ICANS occurred in 10% of tarlatamab-dlle-treated patients, including events with the preferred terms: ICANS (4.7%), muscular weakness (3.2%), cognitive disorder (0.6%), aphasia (0.6%), depressed level of consciousness (0.4%), seizures (0.4%), encephalopathy (0.4%), and leukoencephalopathy (0.2%).1 There was one fatal reaction of ICANS.1 Recurrent ICANS occurred in 1.5% of patients.1 Of the patients who experienced ICANS, most experienced the event following cycle 1 day 1 (2.5%) and cycle 1 day 8 (3.6%).1 Following day 1, day 8, and day 15 infusions, 1.3%, 1.3% and 0.4% of patients experienced ≥Grade 2 ICANS, respectively.1 The median time to onset of ICANS from the first dose of tarlatamab-dlle was 16 days (range: 1 to 862 days).1 ICANS can occur several weeks following administration of tarlatamab-dlle.1 The median time to resolution of ICANS was 4 days (range: 1 to 40 days).1
The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.1 Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.1
Patients receiving tarlatamab-dlle are at risk of neurologic adverse reactions and ICANS resulting in a depressed level of consciousness.1 Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until neurologic symptoms resolve.1
Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment.1 At the first sign of ICANS, immediately discontinue the infusion, evaluate the patient, and provide supportive therapy based on severity.1 Withhold tarlatamab-dlle or permanently discontinue based on severity.1
Other Warnings and Precautions
Tarlatamab-dlle can cause cytopenias including neutropenia, thrombocytopenia, and anemia.1
In the pooled safety population, decreased neutrophils occurred in 16%, including 9% Grade 3 or 4, of tarlatamab-dlle-treated patients.1 The median time to onset for Grade 3 or 4 neutropenia was 41 days (range: 2 to 306).1 Decreased platelets occurred in 30% of patients, including 2.2% Grade 3 or 4.1 The median time to onset for Grade 3 or 4 decreased platelets was 67 days (range: 3 to 420).1 Decreased hemoglobin occurred in 56% of patients, including 4.7% Grade 3 or 4.1 Febrile neutropenia occurred in 1.5% of patients treated with tarlatamab-dlle.1
Monitor patients for signs and symptoms of cytopenias.1 Perform complete blood counts prior to treatment with tarlatamab-dlle, up through cycle 5 day 15 and then prior to administration of tarlatamab-dlle on day 1 of each cycle starting with cycle 6.1 Based on the severity of cytopenias, temporarily withhold, or permanently discontinue tarlatamab-dlle.1
Tarlatamab-dlle can cause serious infections, including life-threatening and fatal infections.1
In the pooled safety population, infections including opportunistic infections occurred in 43% of patients who received tarlatamab-dlle, including 14% Grade 3 or 4. 1 The most frequent infections were pneumonia (11%), urinary tract infection (9%), COVID-19 (6%), upper respiratory tract infection (4.7%), respiratory tract infection (4%), candida infection (2.1%), oral candidiasis (2.1%), and nasopharyngitis (2.1%).1
Monitor patients for signs and symptoms of infection prior to and during treatment with tarlatamab-dlle and treat as clinically indicated.1 Withhold or permanently discontinue the drug based on severity.1
Tarlatamab-dlle can cause hepatotoxicity.1
In the pooled safety population, elevated ALT occurred in 39% of patients who received tarlatamab-dlle, including 2.5% Grade 3 or 4 ALT.1 Elevated AST occurred in 43% of patients, including 3.2% Grade 3 or 4.1 Elevated bilirubin occurred in 16% of patients, with Grade 3 or 4 total bilirubin elevations occurring in 1.3% of patients.1 Liver enzyme elevation can occur with or without concurrent CRS.1
Monitor liver enzymes and bilirubin prior to treatment with tarlatamab-dlle, and as clinically indicated.1 Withhold tarlatamab-dlle or permanently discontinue based on severity.1
Tarlatamab-dlle can cause severe hypersensitivity reactions.1
Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm.1
Monitor patients for signs and symptoms of hypersensitivity during treatment with tarlatamab-dlle and manage as clinically indicated.1 Withhold or consider permanent discontinuation of therapy based on severity.1
Fetal/Neonatal Morbidity and Mortality
Based on its mechanism of action, tarlatamab-dlle may cause fetal harm when administered to a pregnant woman.1, 10 Advise patients of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with tarlatamab-dlle and for 2 months after the last dose.1
During a 3-year evaluation period, 8% (36 out of 445) of patients who received the recommended step-up and full dose of tarlatamab-dlle developed treatment-emergent anti-drug antibodies (ADA).1 In 2 studies, 38% (11 out of 29) of patients who developed treatment-emergent ADA also developed neutralizing antibodies.1 ADA resulted in a 14% increase in the clearance of tarlatamab-dlle.1 Due to the low occurrence of ADA, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and effectiveness of tarlatamab-dlle is unknown.1, 10
Based on its mechanism of action, tarlatamab-dlle may cause fetal harm when administered to a pregnant woman.1 There are no available data on the use of tarlatamab-dlle in pregnant women to inform a drug-associated risk.1
Tarlatamab-dlle causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.1 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.1 Advise women of the potential risk to the fetus.1
There are no data on the presence of tarlatamab-dlle in human milk or the effects on the breastfed child or on milk production.1 The effects of local GI exposure and limited systemic exposure in the breastfed child to tarlatamab-dlle are unknown.1 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.1
Females and Males of Reproductive Potential
Tarlatamab-dlle may cause fetal harm when administered to a pregnant woman.1 Verify pregnancy status of females of reproductive potential prior to initiating tarlatamab-dlle.1
Advise females of reproductive potential to use effective contraception during treatment with tarlatamab-dlle and for 2 months after the last dose.1
The safety and effectiveness of tarlatamab-dlle have not been established in pediatric patients.1
Of the 187 patients with small cell lung cancer (SCLC) who received tarlatamab-dlle 10 mg as a single agent, 51% were 65 years of age or older and 11% were 75 years of age or older.1 No overall differences in tarlatamab pharmacokinetics or safety were observed between older (≥65 years of age) and younger patients.1
The most common adverse reactions (>20%) to tarlatamab-dlle were cytokine release syndrome, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.1
The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased lymphocytes, decreased sodium, decreased total neutrophils, and increased uric acid.1
Tarlatamab-dlle causes transient release of cytokines that may suppress CYP enzymes and result in increased exposure of concomitant CYP substrates during and up to 14 days after occurrence of CRS.1, 10 The risk of drug interactions with concomitant CYP substrates appears to be low.10
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.1, 10 Tarlatamab-dlle causes T-cell activation, release of inflammatory cytokines, and lysis of DLL3-expressing cells.1, 10 Tarlatamab-dlle exhibits anti-tumor activity in mouse models of small cell lung cancer (SCLC).1
Steady state concentrations of tarlatamab-dlle are achieved by cycle 2 day 15.1 The half-life of tarlatamab-dlle is 11 days.1, 10 Tarlatamab-dlle is expected to be metabolized into small peptides by catabolic pathways.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
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.
Tarlatamab-dlle is obtained through designated distributors.2 Contact manufacturer or consult the tarlatamab-dlle website ([Web]) for specific availability information.2
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IV infusion | 1 mg | Imdelltra® | Amgen |
10 mg | Imdelltra® | Amgen |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions April 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Amgen Inc. IMDELLTRA (AMG757)®(Tarlatamab-dlle) prescribing information. Thousand Oaks, CA; 2025 November.
2. Amgen. IMDELLTRA®: Access and reimbursement. From Amgen website. Accessed 2025 Dec 3.
3. Mountzios G, Sun L, Cho BC, Demirci U, Baka S, Gümüs M, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med 2025;393:349-61.
4. Ahn MJ, Cho BC, Felip E, Korantzis I, Ohaski K, Majem M, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med 2023;389:2063-75.
5. American Cancer Society. Treating small cell lung cancer. Accessed 2025 Dec 27. Updates may be available at American Cancer Society website.
6. Kalemkerian GP, Khurshid H, Ismaila N. Systemic therapy for small cell lung cancer: ASCO guideline rapid recommendation update. J Clin Oncol 2024;43:101-105.
7. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 Dec 6.
8. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers 2021;7(1):3.
9. Food and Drug Administration. Application number 761344Orig1s000. Administrative and Correspondence Documents. From FDA website.
10. Food and Drug Administration. Application number 761344Orig1s000. Multi-Discipline Review. From FDA website.