IMDYLLTRA is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after at least two prior lines of therapy including platinum-based chemotherapy.

Treatment with IMDYLLTRA should be initiated and supervised by physicians experienced in the treatment of small cell lung cancer.

IMDYLLTRA should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) (see Section 4.4).

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.

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. Instruct patients and/or caregiver on 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 5. 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. Patients who experience Grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygen) should be monitored with continuous cardiac telemetry and pulse oximetry. 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. Guidelines for Grading and Dosage Modification and Management of Cytokine Release Syndrome^a

^a CRS based on American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (2019).

^b See section 4.2.1, Table 3 for recommendations on restarting IMDYLLTRA after dose delays.

^c Taper steroids per standard of care guidelines.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Monitor patient for signs and symptoms of ICANS. Rule out other causes of neurologic symptoms. Provide intensive care for severe or life-threatening neurologic toxicities. If ICANS is suspected, manage according to the recommendations in Table 3.

Table 3. Guidelines for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome^a

Table 4. Recommended Treatment Interruptions of IMDYLLTRA for the Management of Cytopenias, and Other Adverse Reactions

^a Refer to Table 4 for dose restarting guidance.

^b Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

Restarting IMDYLLTRA After Dosage Delay

If a dose of IMDYLLTRA is delayed, restart therapy based on the recommendations listed in Table 5 and resume the dosing schedule accordingly (see Table 1). Administer required concomitant medications as indicated in section 4.2.

Table 5. Recommendations for Restarting Therapy with IMDYLLTRA After Dosage Delay

^a Administer required concomitant medications before and after Day 1 and Day 8 of IMDYLLTRA infusions and monitor patients accordingly (see section 4.2).

Special populations

Elderly

In clinical studies, no overall differences in tarlatamab pharmacokinetics, safety or efficacy were observed between elderly patients (≥ 65 years of age) and younger patients. No dose adjustment is necessary in elderly patients (≥ 65 years of age).

Hepatic Impairment

Based on population pharmacokinetic analyses, no dose adjustment is required in patients with mild hepatic impairment. IMDYLLTRA has not been studied in patients with moderate or severe hepatic impairment.

Renal impairment

Based on population pharmacokinetic analyses, no dose adjustment is required in patients with mild or moderate renal impairment. IMDYLLTRA has not been studied in patients with severe renal impairment.

Paediatric population

The safety and efficacy of IMDYLLTRA in children aged ≤ 18 years of age have not yet been established.

Method of administration

IMDYLLTRA is for intravenous use.

IV line for premedication can be used for IMDYLLTRA. IV-line flush should be administered over 3-5 minutes using 0.9% Sodium Chloride for Injection.

Administer the entire contents of IMDYLLTRA as an intravenous infusion over 1 hour at a constant flow rate using an infusion pump. The pump should be programmable, lockable, non-elastomeric, and have an alarm (see section 6.6). IV tubing is primed with 0.9% Sodium Chloride for Injection, OR final prepared IMDYLLTRA.

IMDYLLTRA should be infused over 1 hour at an infusion rate of 250mL/hour, see Table 6.

Table 6. IMDYLLTRA Administration Information

For instructions on the handling and preparation of the medicinal product before administration, see section 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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.

Cytokine Release Syndrome (CRS)

Administration of IMDYLLTRA has been associated with cytokine release syndrome (CRS) which may be serious or life-threatening (see section 4.8). 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. Section 4.2.Patients should be closely monitored for signs and symptoms of CRS during the initiation of IMDYLLTRA treatment.

At the first sign of CRS, immediately interrupt IMDYLLTRA infusion,

evaluate the patient for hospitalisation and institute supportive care based on severity. Management of these events may require the dose to be either modified or permanently discontinued (see section 4.2). 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 Neutropenia.

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. Withhold or consider permanent discontinuation of IMDYLLTRA based on severity (see sections 4.2).

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, before each dose, and 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, before each dose, and as clinically indicated.

Withhold IMDYLLTRA or permanently discontinue based on severity as clinically indicated.

No formal drug interaction studies have been conducted with IMDYLLTRA. Initiation of IMDYLLTRA treatment causes transient release of cytokines that may suppress CYP450 enzymes and may result in increased exposures of concomitant CYP substrates. In patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index e.g., sirolimus and tacromilus, monitor for known adverse events. Adjust the dose of the concomitant drug as needed.

Pregnancy

There are no data from the use of tarlatamab in pregnant women.

Breast-feeding

It is unknown whether tarlatamab is excreted in human milk. Because many medicinal products, including antibodies, can be secreted in human milk, a risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue IMDYLLTRA treatment taking into account the benefit of breast-feeding for the child and the benefit of IMDYLLTRA treatment for the woman.

Fertility

No studies have been conducted to evaluate the effects of tarlatamab on fertility.

Studies on the effects of IMDYLLTRA on the ability to drive and use machines have not been performed. However, due to the potential for ICANS associated neurological events, following tarlatamab infusion, 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.

Summary of the safety profile

The safety of IMDYLLTRA was evaluated in 160 patients with metastatic small cell lung cancer (SCLC) who received 10 mg as monotherapy. The medium duration of exposure to IMDYLLTRA was 14.14 weeks (range: 0.1 to 93.4).

The most common adverse reactions were cytokine release syndrome (53.8%), pyrexia (36.9%), dysgeusia (30%), decreased appetite (29.4%), constipation (27.5%), fatigue (26.9%), anaemia (25%), and asthenia (21.9%).

Tabulated list of adverse reactions

Adverse reactions reported in IMDYLLTRA clinical studies are displayed in Table 7 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 7. Adverse reactions

^a Adverse reactions for IMDYLLTRA occurring at doses other than the 10 mg dose in monotherapy cohorts.

^b Additional information is provided in “ Descriptions of selected adverse reactions” .

Description of selected adverse reactions

Cytokine release syndrome (CRS)

In clinical trials with pooled safety data for 160 patients with SCLC enrolled in DeLLphi-300 and DeLLphi-301, receiving the IMDYLLTRA 10 mg dose, CRS occurred in 53.8% of patients, with Grade 1 in 32.5%, Grade 2 in 20% of patients, Grade 3 in 0.6% of patients and grade 4 events in 0.6% of patients. No patients had grade 5 events. Serious events of CRS were reported in 23.1% of patients. After the first dose of IMDYLLTRA, 41.3% of patients experienced CRS, with 28.8% of patients experiencing any grade CRS after the second dose. The majority of CRS events occurred after the first two doses, with 8.8% of patients experiencing CRS following third dose or later. Following the Day 1 infusion, 15.6% of patients experienced ≥ Grade 2 CRS. Following the Day 8 infusion, 4.4% of patients experienced ≥ Grade 2 CRS. The median time from the first dose of IMDYLLTRA to the first onset of CRS was 2 days (range: 1 to 25 days).

In patients treated with IMDYLLTRA at 10 mg enrolled in Study DeLLphi-301 (n=133), CRS occurred in 52.6% of patients, including Grade 1 in 31.6%, Grade 2 in 20.3 % and Grade 3 in 0.8% of patients. No patients had Grade 4 or Grade 5 events. Most patients experienced CRS after the first two doses of IMDYLLTRA with 9.8% experiencing CRS after the third dose or later. Following the Day 1 infusion, 16.5% of patients experienced ≥ Grade 2 CRS. Following the Day 8 infusion, 3.0% of patients experienced ≥ Grade 2 CRS. Median time to onset of first CSR symptom was 15.5 hours. For those Grade 1 events that progressed to Grade 2 or greater, the median time from Grade 1 event to Grade 2 event is 22.1 hours.

ICANS

In clinical trials with pooled safety data for 160 patients with SCLC enrolled in Study DeLLphi-300 and Study DeLLphi-301 receiving IMDYLLTRA 10 mg dose, ICANS was reported in 9.4% of patients. The median time from the first dose of IMDYLLTRA to the first onset of ICANS was 30 days (range: 1 to 15 days). The median time to resolution of ICANS was 33 days (range: 1 to 93 days).

Neutropenia

In clinical trials with pooled safety data for 160 patients with SCLC enrolled in Study DeLLphi-300 and Study DeLLphi-301 receiving IMDYLLTRA 10 mg dose, neutropenia occurred in 14.4% of patients including Grade 3 or higher events in 6.3% of patients and Grade 4 events in 2.5% of patients. The median time from the first dose of IMDYLLTRA to the first onset of neutropenia was 43 days (range: 3 to 244 days). Neutropenia leading to dose interruption occurred in 0.6% 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-drug antibodies in other studies, including those of tarlatamab or of other DLL3 T-cell engager products.

Across Study DeLLphi-300 and Study DeLLphi-301, the incidence of anti-tarlatamab antibody development was 4.7% (7/149) in patients receiving the dose of 10 mg. In the phase 2 Study DeLLphi-301 which employed the neutralising assay, none of the patients developed neutralising antibodies. Positive anti-tarlatamab antibody binding status had no clinically relevant impact on efficacy and safety.

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. Healthcare professionals are asked to report any suspected adverse reactions via

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

There is no clinical experience with overdose with IMDYLLTRA. Doses up to 100 mg every two weeks and 200 mg every three weeks have been administered in clinical trials. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required.

Pharmacotherapeutic group: Other monoclonal antibodies and antibody drug conjugates, ATC code: L01FX33.

Mechanism of action

IMDYLLTRA is a bispecific DLL3-directed CD3 T-cell engager that binds to DLL3 expressed on the surface of tumor cells and CD3 expressed on the surface of T cells. The bispecific binding of tarlatamab to T cells and DLL3-positive tumour cells triggers T-cell activation, production of inflammatory cytokines, release of cytotoxic proteins, which results in redirected lysis of tumour cells.

Pharmacodynamic effects

The pharmacodynamic response after a single infusion of tarlatamab was characterised by T-cell redistribution and activation, and transient cytokine elevation. Peripheral T-cell redistribution (i.e., T-cell adhesion to blood vessel endothelium and/or transmigration into tissue) occurred within 24 hours after the initial dose of tarlatamab at 1 mg on Day 1. T-cell counts declined within 6 hours post infusion and returned to baseline levels in majority of the patients prior to the next infusion on Day 8.

Serum cytokines IL-2, IL-6, IL-8, IL-10, IFN-γ and TNF-α were transiently elevated following the initial dose of tarlatamab at 1 mg on Day 1. Cytokine levels peaked within the first 2 days following the start of tarlatamab infusion and generally returned to baseline levels prior to the next infusion on Day 8. In subsequent treatments, cytokine elevation occurred in fewer patients with lesser intensity compared to the initial infusion on Day 1.

Clinical efficacy and safety

The efficacy of IMDYLLTRA was demonstrated in patients enrolled in a phase 2, open label multicentre trial, Study DeLLphi-301. Eligible patients were required to have extensive-stage SCLC with disease progression after receiving previous treatment including platinum-based chemotherapy, an ECOG Performance Status of 0-1, and at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours (RECIST v1.1). The trials excluded patients with symptomatic brain metastases, evidence of interstitial lung disease or non-infectious pneumonitis and active immunodeficiency.

Study DeLLphi-301 Part 1 was a dose comparison that randomised 176 patients in a 1:1 ratio to receive either 10 mg or 100 mg of tarlatamab (as a 60-minute intravenous (IV) infusion). At the prespecified interim analysis, 30 patients per arm were used to determine the selected dose for part 2. Part 2 was a dose expansion that enrolled 100 patients (part 1 and 2 combined) at the selected dose of 10 mg. A total of 99 patients received tarlatamab 10 mg intravenously every 2 weeks across Part 1 and Part 2 (combined), and a total of 87 patients received tarlatamab 100 mg intravenously every 2 weeks in Part 1. Treatment continued until disease progression or unacceptable toxicity. Tumour assessments were performed every 6 weeks for the first 48 weeks and every 12 weeks thereafter.

The key efficacy outcome measures were ORR and DOR as assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1.

For patients who received tarlatamab 10 mg, the baseline demographics and disease characteristics of the study population were: median age of 64 years (range: 35 to 82); 48.5% age 65 or older; 71.7% male; 57.6% White and 41.4% Asian; 26.3% ECOG PS of 0 and 73.7% ECOG PS of 1; 2% had M0 disease and 98% had M1 disease; and 22.2% had a history of brain metastases. 100% received prior platinum therapy, 20.2% received prior topotecan therapy, 69.7% received prior anti- PD-L1 therapy;8.1% had never smoked, 73.7% formerly smoked, and 18.2% currently smoked. Time to progression was < 90 days for 27/69 (39.1%) subjects and ≥ 90 days for 42/69 (60.9%) subjects.

ORR and DOR were generally similar to the total population in the subgroups that had < 90 or ≥ 90 days to progression after first line platinum therapy. Efficacy results are summarised in Table 8.

Table 8. Efficacy Results for patients with SCLC Who Received IMDYLLTRA 10 mg

*Assessed by Blinded Independent Central Review

** Observed proportion of responders beyond the 6-month landmark.

^a Assessed by Blinded Independent Central Review, CI = Confidence Interval

^b Median based on Kaplan-Meier estimate.

^c Observed proportion of responders beyond the 6-month landmark.

^d Observed proportion of responders beyond the 9-month landmark.

^e Observed proportion of responders beyond the 12-month landmark.

^f DOR based on DCO of Jan 12, 2024.

Paediatric population

The Medicines and Healthcare products Regulatory Agency has waived the obligation to submit the results of studies with IMDYLLTRA in all subsets of the paediatric population in SCLC (see section 4.2 for information on paediatric use).

Conditional approval

This medicinal product has been authorised under a so-called 'conditional approval' scheme. This means that further evidence on this medicinal product is awaited. The Medicines and Healthcare products Regulatory Agency will review new information on this medicinal product at least every year and this SmPC will be updated as necessary.

The peak serum concentration (C_max), trough serum concentrations (C_trough) and area under the serum concentration versus time curve at steady state (AUC_tau), of tarlatamab increased dose proportionally in the evaluated dose range of 0.3 mg to 100 mg Q2W. Approximate steady state in serum tarlatamab exposures were achieved by Day 28.

Distribution

The geometric mean value (CV%) for volume of distribution at steady state is 8.6 L (18.3%).

Biotransformation

The metabolic pathway of tarlatamab has not been characterised. Like other protein therapeutics, tarlatamab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Elimination

The estimated systemic clearance (inter-subject CV%) was 0.65 L/day (44%) and terminal elimination half-life was approximately 11.2 days in subjects with SCLC.

Pharmacokinetics in special populations

No clinically meaningful differences in the clearance of tarlatamab were observed based on age, bodyweight, sex, race, mild or moderate renal impairment (eGFR ≥ 30 mL/min), or mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and AST > ULN). The intra-individual variability was estimated by population PK analysis to be 57.5%.

Carcinogenicity

No carcinogenicity or genotoxicity studies have been conducted with tarlatamab.

Impairment of Fertility

No studies have been conducted to evaluate the effects of tarlatamab on fertility.

Reproductive toxicity

There are no available data from the use of tarlatamab in pregnant women. Based on its mechanism of action, tarlatamab may cause foetal harm when administered to a pregnant woman. In a murine embryo-foetal development study, there were no effects of the murine surrogate molecule of tarlatamab, designated muS757, on any maternal parameter, including mean maternal body weights or body weight gains. In addition, there were no muS757-related macroscopic findings or effects on any ovarian, uterine, or litter parameters at any dose level and administration of muS757 did not produce any foetal external, visceral, or skeletal malformations or variations.

Powder

L-glutamic acid

Sucrose

Polysorbate 80

Sodium hydroxide

IV Solution stabiliser (IVSS)

Citric acid monohydrate (E330)

Lysine hydrochloride

Polysorbate 80

Sodium hydroxide (for pH adjustment)

Water for injections

No known incompatibilities.

Unopened vial

36 months.

The information in Table 9 indicates the storage time for the reconstituted IMDYLLTRA infusion bag. Store lyophilized IMDYLLTRA and IV Solution Stabiliser (IVSS) for a maximum of 24 hours at room temperature in the original carton to protect from light.

Table 9. Maximum Storage Time

*Storage time includes total time permitted from point of reconstitution of the vial to the end of administration. If the prepared IMDYLLTRA infusion bag is not administered within the time frames and temperatures indicated, it must be discarded; it should not be refrigerated again.

Store and transport refrigerated (2° C to 8° C).

Do not freeze.

Store the vials in the original packaging in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

IMDYLLTRA consists of two packaging configurations:

• 1 mg packaging contains 1 vial of 1 mg tarlatamab and 2 vials of 7 mL IV Solution Stabiliser

• 10 mg packaging contains 1 vial of 10 mg tarlatamab and 2 vials of 7 mL IV Solution Stabiliser

Sterile Water for Injection, (not included) should be used to reconstitute IMDYLLTRA.

The IV Solution Stabiliser is used to coat the intravenous bag prior to addition of reconstituted IMDYLLTRA to prevent adsorption of IMDYLLTRA to IV bags and IV tubing.

IMDYLLTRA should be reconstituted without the use of IV Solution Stabiliser (IVSS).

Aseptic preparation

Strictly observe aseptic technique when preparing the solution for infusion since IMDYLLTRA vials do not contain antimicrobial preservatives. Reconstitution of IMDYLLTRA is with Sterile Water for Injection.

Other instructions

IMDYLLTRA is compatible with polyolefin, PVC or ethyl vinyl acetate (EVA) infusion bags at the specified administration conditions.

IV line and catheter materials composed of polyolefin, PVC and polyurethane have been shown to be compatible with IMDYLLTRA at the specified administration conditions.

The use of Closed System Transfer Device (CSTD) is not required when preparing IMDYLLTRA and currently Amgen cannot provide guidance on, nor recommend for or against, their use.

The empty IV bag and IV tubing should be disposed of in accordance with local requirements.

Table 10. Required amount of Sterile Water for Injection (SWFI) to Reconstitute IMDYLLTRA^a

^a Vial contains overfull to ensure delivery at the stated concentration of labelled vial strength.

1. Transfer required amount of Sterile Water for Injection (refer to table 10) into the IMDYLLTRA vial to provide a final IMDYLLTRA concentration of 0.9 mg/mL (1 mg vial) or 2.4 mg/mL (10 mg vial). Direct Sterile Water for Injection along the walls of the IMDYLLTRA vial and not directly on the lyophilized powder.

• IV Solution Stabiliser should not be used to reconstitute IMDYLLTRA.

2. Gently swirl contents. Do not shake.

3. Inspect that the solution is clear to slightly opalescent, colourless to slightly yellow. Do not use if solution is cloudy or has particulates.

Preparation of IMDYLLTRA

Table 11. Preparation Guide for 1-hour infusion

*Note: the final concentrations for the different strength vials are NOT the same following reconstitution.

1. Withdraw 0.9% Sodium Chloride for Injection.

a. Withdraw the required volume from a pre-filled 250 mL 0.9% Sodium Chloride bag. Refer to Table 11. Disregard any overfill in the IV bag.

2. Add IV Solution Stabiliser (IVSS).

a. Transfer 13 mL of IVSS to the IV bag containing 0.9% Sodium Chloride for Injection.

b. Gently mix the contents of the bad to avoid foaming. Do not shake.

3. Add reconstituted IMDYLLTRA.

a. Transfer the required volume of reconstituted IMDYLLTRA into the stabilised IV bag containing 0.9% Sodium Chloride for Injection and IVSS. Refer to Table 11.

b. Gently mix the contents of the bag to avoid foaming. Do not shake.

4. Remove the air from the IV bag.

5. Prime IV tubing separately with 0.9% Sodium Chloride for Injection OR final prepared product.

Disposal

The release of pharmaceuticals into the environment should be minimised. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.