IMDYLLTRA

Treatment with IMDYLLTRA should be initiated and supervised by physicians experienced in the treatment of small cell lung cancer. 4). Posology Pre-treatment medicinal products should be administered prior to each dose of IMDYLLTRA on Day 1 and Day 8 of the dosing schedule (see below).

Recommended dosing Schedule The recommended dosage and schedule of IMDYLLTRA is an initial dose of 1 mg on Day 1 followed by 10 mg on Days 8, 15, and every 2 weeks thereafter as shown in Table 1. Table 1. IMDYLLTRA recommended dosage and schedule.

Dose of IMDYLLTRA Day 1 1 mg Day 8 10 mg Day 15 and every 2 weeks thereafter 10 mg Administer IMDYLLTRA as a 1-hour intravenous infusion in an appropriate healthcare setting. Ensure patients are well hydrated prior to administration of IMDYLLTRA.

Premedicate with dexamethasone 8 mg IV 1 hour prior to first two doses (Day 1 and Day 8). Consider IV fluids for patients after infusion of IMDYLLTRA (Day 1 and Day 8). Monitor patients during the infusion and for at least 16 hours after the first infusion (Day 1).

On Day 8, monitor patients for 6-8 hours post infusion and at subsequent infusions monitor patients for 2-4 hours post infusion at the discretion of the healthcare professional. On Day 1 and Day 8, recommend patients to remain within 1 hour of an appropriate healthcare setting, such as the treatment hospital, for 24 hours starting from each IMDYLLTRA infusion, 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. Duration of treatment Administer IMDYLLTRA until disease progression or unacceptable toxicity.

Dose modifications and Adverse Reaction Management If a dose of IMDYLLTRA is delayed because of an adverse event, therapy will be restarted based on the recommendations listed in Table 6. See Table 2 and Table 3 for recommended actions for the management of CRS and ICANS respectively and Table 4 for neutropenia and other adverse reactions.

Cytokine Release Syndrome (CRS) Diagnose CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. If CRS is suspected, manage according to the recommendations in Table 2. , hypotension not responsive to fluids, or hypoxia requiring supplemental oxygen) should be monitored for signs and symptoms of CRS including fever, hypotension and hypoxia using pulse oximetry or cardiac telemetry as indicated.

For severe or life- threatening CRS, recommend anti-IL-6 therapy, for example, tocilizumab and admission in an intensive-care unit (ICU) for supportive therapy. Table 2 provides the guidelines for grading and dosage modification and management of cytokine release syndrome.

Table 2. , fever ≥ 38°C without hypotension or hypoxia). Withhold IMDYLLTRA until event resolves, then resume IMDYLLTRA at the next scheduled doseb. , paracetamol) for fever. • Consider dexamethasonec 4 mg (or equivalent) to 10 mg PO or IV.

Grade 2 Symptoms require and respond to moderate intervention. Fever ≥38°C, Hypote Withhold IMDYLLTRA until event resolves, then resume IMDYLLTRA at the next scheduled • Recommend hospitalisation with monitoring for fever, hypotension and hypoxia using pulse oximetry or cardiac telemetry as indicated.

• Administer symptomatic CRS Grade Defining Symptoms IMDYLLTRA Dosage Modification Management nsion responsive to fluids not requiring vasopressors, and/or Hypoxi a requiring low flow nasal cannula or blow-by. doseb. , paracetamol) for fever.

• Administer supplemental oxygen and intravenous fluids when indicated. i • Consider tocilizumab (or equivalent). When resuming treatment at the next planned dose, monitor patients at the physician’s discretion in an appropriate healthcare settingb.

Grade 3 Severe symptoms defined as temperature ≥ 38°C with:

Haemo dynamic instability requiring a vasopressor (with or without vasopressin) or Worsen ing hypoxia or respiratory distress requiring high flow nasal canula (> 6 L/min oxygen) or face mask. Withhold IMDYLLTRA until the event resolves, then resume IMDYLLTRA at the next scheduled doseb.

For recurrent Grade 3 events, permanently discontinue IMDYLLTRA. , ICU care. • Administer dexamethasonec (or equivalent) 8 mg IV every 8 hours up to 3 doses. • 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 Day 1 and Day 8 (see Table 1).

When resuming treatment at the next planned dose, monitor patients at the physician’s discretion in an appropriate healthcare settingb. CRS Grade Defining Symptoms IMDYLLTRA Dosage Modification Management Grade 4 Life- threatening symptoms defined as temperature ≥38°C with: Haemo dynamic instability requiring multiple vasopressors (excluding vasopressin).

Worsen ing hypoxia or respiratory distress despite oxygen administration requiring positive pressure. Permanently discontinue IMDYLLTRA. • ICU care. • Grade 3 treatment. a CRS based on American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (2019).

2, Table 5 for recommendations on restarting IMDYLLTRA after dose delays. c Taper […]

Summary of the safety profile The safety of IMDYLLTRA, based on pooled data from Study DeLLphi-300, and Study DeLLphi-301 and Study DeLLphi-304, was evaluated in 473 patients with small cell lung cancer (SCLC) who received 10 mg as monotherapy.

The median duration of exposure to IMDYLLTRA was 18 weeks (range: 6 to 38). 0%). Tabulated list of adverse reactions Adverse reactions reported in IMDYLLTRA clinical studies are displayed in Table 8 below. Frequency is provided by MedDRA category: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 and < 1/1,000), very rare (< 10,000).

Within each system organ class, adverse reactions are presented in order of decreasing seriousness. Table 8. Adverse reactions MedDRA system organ class Very Common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥ 1/1,000 to < 1/100) Blood and lymphatic systems disorders Anaemia Neutropeniaa, c Lymphopeniab Gastrointestinal disorders Constipation Nausea General disorders and administration site conditions Pyrexia Fatigue Asthenia Immune system disorders Cytokine release syndrome b Metabolism and nutrition disorders Decreased appetite Hyponatraemia Nervous system disorders Dysgeusia Headache Immune effector cell-associated neurotoxicity syndrome c Tremor Neurotoxicity Seizure Ataxia Encephalopathy Psychiatric disorders Confusional state Delirium Respiratory, thoracic, and mediastinal disorders Dyspnoea Investigations Weight decreased a Includes neutropenia and neutrophil count decreased.

b Includes lymphopenia and lymphocyte count decreased. c Additional information is provided in “Descriptions of selected adverse reactions”. 2% of patients. No patients had Grade 5 events. 7% of patients. 4% of patients experienced any grade CRS, with 34% of patients experiencing any grade CRS after the second dose.

5% of patients experiencing CRS following third dose or later. 7% of patients experienced ≥ Grade 2 CRS. 4% of patients experienced ≥ Grade 2 CRS. 5 hours). 2% of patients. No patients had Grade 4 or Grade 5 events. 3% experiencing CRS after the third dose or later.

5% of patients experienced ≥ Grade 2 CRS. 8% of patients experienced ≥ Grade 2 CRS. 1 hours). 7% of patients. 0 days (range: 2 to 13 days). The median time to resolution of ICANS was 4 days (range: 2 to 8 days). 2% of patients experiencing Grade 3 and Grade 4 events.

The median time from the first dose of IMDYLLTRA to the first onset of neutropenia was 43 days (range: 29 to 109 days). 9% patients with none leading to treatment discontinuation. Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-tarlatamab antibodies in other studies, including those of tarlatamab or of other DLL3 T-cell engager products.

7% (34/444) in patients receiving the dose of 10 mg. 1% (11/359) of patients developed anti-tarlatamab neutralising antibodies. Positive anti-tarlatamab antibody status had no clinically relevant impact on efficacy, safety and pharmacokinetics.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 8). CRS may be associated with symptoms including pyrexia, hypotension, fatigue, hypoxia, tachycardia, headache, chills, nausea, and vomiting.

The majority of these events did not lead to IMDYLLTRA discontinuation in clinical trials. 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 IMDYLLTRA in a healthcare setting equipped to monitor and manage CRS. Ensure patients are euvolemic prior to initiating the infusions. 2. Patients should be closely monitored for signs and symptoms of CRS during the initiation of IMDYLLTRA treatment.

To mitigate the risk of CRS, it is important to initiate IMDYLLTRA at the recommended starting dose in Table 1. CRS should be managed according to the recommendations in Table 2. At the first sign of CRS, immediately interrupt IMDYLLTRA infusion, evaluate the patient for hospitalisation and institute supportive care based on severity.

2). Counsel patients to seek medical attention should signs or symptoms of CRS occur. Immune effector cell-associated neurotoxicity syndrome (ICANS) Administration of IMDYLLTRA has been associated with ICANS which may be serious or life-threatening.

ICANS can occur up to several weeks following administration of IMDYLLTRA. Adverse events that may be associated with ICANS include headache, encephalopathy, confusion, delirium, seizure, ataxia, neurotoxicity, and tremor. Patients should be closely monitored for signs and symptoms of ICANS during IMDYLLTRA treatment.

ICANS should be managed according to the recommendations in Table 3. CNS metastases There is limited experience of IMDYLLTRA in patients with central nervous system (CNS) involvement. The risk/benefit of IMDYLLTRA has not been established in patients with active brain metastases.

The overall safety profile was similar for patients with or without a history of active CNS metastases. Hypersensitivity Hypersensitivity reactions have been reported in patients treated with IMDYLLTRA including rare severe events. 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 IMDYLLTRA and manage as clinically indicated. 2). Cytopenias IMDYLLTRA can cause cytopenias including neutropenia, thrombocytopenia, and anaemia. Monitor patients for signs and symptoms of cytopenias.

Perform complete blood counts prior to treatment with IMDYLLTRA, as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDYLLTRA as clinically indicated. Elevated Liver Tests IMDYLLTRA can cause transient elevation of liver enzymes.

Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDYLLTRA, as clinically indicated. Withhold IMDYLLTRA or permanently discontinue based on severity as clinically indicated.

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