IMDELLTRA

Generic Name/API: (AMG757)- tarlatamab-dlle

Manufacturer: Amgen

Dosage Forms & Strength & Pack Size:
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.

Storage:
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.

  • INDICATION
  • IMPORTANT SAFETY INFORMATION

Indication
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) 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).

WARNINGS AND PRECAUTIONS
Cytokine Release Syndrome
IMDELLTRA can cause cytokine release syndrome (CRS) including serious or lifethreatening reactions. In the pooled safety population [see Adverse Reactions (6.1)], CRS occurred in 55% of patients who received IMDELLTRA, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of IMDELLTRA-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, 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 IMDELLTRA was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA 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 IMDELLTRA following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA infusions as described in Table 3 to reduce the risk of CRS [see Dosage and Administration (2.3)]. Administer IMDELLTRA in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA. Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA. At the first sign of CRS, immediately discontinue IMDELLTRA infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA based on severity [see Dosage and
Administration (2.5)]. Counsel patients to seek medical attention should signs if symptoms of CRS occur.

Neurologic Toxicity Including ICANS
IMDELLTRA can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population [see Adverse Reactions (6.1)], neurologic toxicity including ICANS, occurred in 47% of patients who received IMDELLTRA, 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 IMDELLTRA-treated patients [see Adverse Reactions (6.1)]. 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 IMDELLTRA was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRA. 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 IMDELLTRA 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 IMDELLTRA or permanently discontinue based on severity [see Dosage and Administration (2.5)].

Cytopenias
IMDELLTRA can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, [see Adverse Reactions (6.1)], decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRA-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% 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% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRA. Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA [see Dosage and Administration (2.5)].

Infections
IMDELLTRA can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, [see Adverse Reactions (6.1)], infections including opportunistic infections occurred in 41% of patients who received IMDELLTRA. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID19 (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
IMDELLTRA and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA based on severity [see Dosage and Administration (2.5)].

Hepatotoxicity
IMDELLTRA can cause hepatotoxicity.
In the pooled safety population [see Adverse Reactions (6.1)], elevated ALT occurred in 42% with Grade 3 or 4 ALT elevation occurring in 2.1% of IMDELLTRA-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 occurred in 1.6% of patients [see Adverse Reactions (6.1)]. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA, before each dose, and as clinically indicated.
Withhold IMDELLTRA or permanently discontinue based on severity [see Dosage and Administration (2.5)].

Hypersensitivity
IMDELLTRA 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 IMDELLTRA and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA based on severity [see Dosage and Administration (2.5)].

Embryo-Fetal Toxicity
Based on its mechanism of action, IMDELLTRA 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 IMDELLTRA and for 2 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

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